Constraint field descriptions Descriptions of columns in the gnomAD v4 constraint metrics tsv. Descriptions also apply to rows in Hail Tables, where a “.” in the field name indicates a struct: -gene: Gene name -transcript: Ensembl or RefSeq transcript ID -canonical: Boolean indicator as to whether the transcript is the canonical transcript for the gene -mane_select: Boolean indicator as to whether the transcript is the MANE Select transcript for the gene -lof_hc_lc.obs: Number of observed high and low confidence loss-of-function (pLoF) variants in transcript -lof_hc_lc.exp: Number of expected high and low confidence pLoF variants in transcript -lof_hc_lc.possible: Number of possible high and low confidence pLoF variants in transcript -lof_hc_lc.oe: Observed over expected ratio for high and low confidence pLoF variants in transcript (lof_hc_lc.obs divided lof_hc_lcy lof.exp) -lof_hc_lc.mu: Mutation rate summed across all possible high and low confidence pLoF variants in transcript -lof_hc_lc.pLI: Probability of loss-of-function intolerance; probability that transcript falls into distribution of haploinsufficient genes (~21% o/e pLoF ratio; computed from high and low confidence pLoF gnomAD data) -lof_hc_lc.pRec: Probability that transcript falls into distribution of recessive genes (~71% o/e pLoF ratio; computed from high and low confidence pLoF gnomAD data) -lof_hc_lc.pNull: Probability that transcript falls into distribution of unconstrained genes (~100% o/e pLoF ratio; computed from high and low confidence pLoF gnomAD data) -lof.obs: Number of observed high confidence loss-of-function (pLoF) variants in transcript -lof.exp: Number of expected high confidence pLoF variants in transcript -lof.possible: Number of possible high confidence pLoF variants in transcript -lof.oe: Observed over expected ratio for high confidence pLoF variants in transcript (lof.obs divided by lof.exp) -lof.mu: Mutation rate summed across all possible high confidence pLoF variants in transcript -lof.pLI: Probability of loss-of-function intolerance; probability that transcript falls into distribution of haploinsufficient genes (~21% o/e pLoF ratio; computed from high confidence pLoF gnomAD data) -lof.pRec: Probability that transcript falls into distribution of recessive genes (~71% o/e pLoF ratio; computed from high confidence pLoF gnomAD data) -lof.pNull: Probability that transcript falls into distribution of unconstrained genes (~100% o/e pLoF ratio; computed from high confidence pLoF gnomAD data) -lof.oe_ci.lower: Lower bound of 90% confidence interval for o/e ratio for high confidence pLoF variants -lof.oe_ci.upper: LOEUF: upper bound of 90% confidence interval for o/e ratio for high confidence pLoF variants (lower values indicate more constrained) -lof.oe_ci.upper_rank: Transcript’s rank of LOEUF value compared to other transcripts (lower values indicate more constrained). This annotation is only applied to MANE Select transcripts unless a gene does not have a MANE Select transcript, in which case the canonical transcript (if available) will be used instead. lof.oe_ci.upper_bin_decile: Decile bin of LOEUF for given transcript (lower values indicate more constrained). This annotation is only applied to MANE Select transcripts unless a gene does not have a MANE Select transcript, in which case the canonical transcript (if available) will be used instead. -lof.z_raw: Raw Z-score for pLoF variants in transcript -lof.z_score: Z-score for pLoF variants in transcript. Higher (more positive) Z scores indicate that the transcript is more intolerant of variation (more constrained) -mis.obs: Number of observed missense variants in transcript -mis.exp: Number of expected missense variants in transcript -mis.possible: Number of possible missense variants in transcript -mis.oe: Observed over expected ratio for missense variants in transcript (mis.obs divided by mis.exp) -mis.mu: Mutation rate summed across all possible missense variants in transcript -mis.oe_ci.lower: Lower bound of 90% confidence interval for o/e ratio for missense variants -mis.oe_ci.upper: Upper bound of 90% confidence interval for o/e ratio for missense variants -mis.z_raw: Raw Z-score for missense variants in transcript -mis.z_score: Z-score for missense variants in transcript. Higher (more positive) Z scores indicate that the transcript is more intolerant of variation (more constrained) -mis_pphen.obs: Number of observed missense variants in transcript predicted "probably damaging" by PolyPhen-2 -mis_pphen.exp: Number of expected missense variants in transcript predicted "probably damaging" by PolyPhen-2 -mis_pphen.possible: Number of possible missense variants in transcript that are predicted "probably damaging" by PolyPhen-2 -mis_pphen.oe: Observed over expected ratio for PolyPhen-2 predicted "probably damaging" missense variants in transcript (mis_pphen.obs divided by mis_pphen.exp) -syn.obs: Number of observed synonymous variants in transcript -syn.exp: Number of expected synonymous variants in transcript -syn.possible: Number of possible synonymous variants in transcript -syn.oe: Observed over expected ratio for missense variants in transcript (syn.obs divided by syn.exp) -syn.mu: Mutation rate summed across all synonymous variants in transcript -syn.oe_ci.lower: Lower bound of 90% confidence interval for o/e ratio for synonymous variants -syn.oe_ci.upper: Upper bound of 90% confidence interval for o/e ratio for synonymous variants -syn.z_raw: Raw Z-score for synonymous variants in transcript -syn.z_score: Z-score for synonymous variants in transcript. Higher (more positive) Z scores indicate that the transcript is more intolerant of variation (more constrained). Extreme values of syn.z_score indicate likely data quality issues -constraint_flags: Reason transcript does not have constraint metrics. One of: –no_variants: Zero observed synonymous, missense, pLoF variants –no_exp_lof: Zero expected pLoF variants –outlier_lof: Number of pLoF variants is significantly different than expectation –no_exp_mis: Zero expected missense variants –outlier_mis: Number of missense variants is significantly different than expectation –no_exp_syn: Zero expected synonymous variants –outlier_syn: Number of synonymous variants is significantly different than expectation -chromosome: Chromosome on which the transcript is located -level: Transcript level from Gencode (https://www.gencodegenes.org/pages/data_format.html) -transcript_type: Transcript biotype (https://www.gencodegenes.org/pages/biotypes.html) -cds_length: Length of the coding sequences (CDS) in the transcript -num_coding_exons: Number of coding exons in the transcript