4-99280921-C-T

Variant names:

• chr4-99280921-C-T
• rs1229976
• NM_000667.4:c.829-642G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000667.4(ADH1A):​c.829-642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,154 control chromosomes in the GnomAD database, including 51,044 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51044 hom., cov: 31)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 8 publications found

Genes affected

ADH1A (HGNC:249): (alcohol dehydrogenase 1A (class I), alpha polypeptide) This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence. [provided by RefSeq, Nov 2010]

ENSG00000246090 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1A	NM_000667.4	c.829-642G>A		intron_variant	Intron 6 of 8	ENST00000209668.3	NP_000658.1
LOC100507053	NR_037884.1	n.3790-5874C>T		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3	c.829-642G>A		intron_variant	Intron 6 of 8	1	NM_000667.4	ENSP00000209668.2

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124112 AN: 152036 Hom.: 50991 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.825

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.816 AC: 124220 AN: 152154 Hom.: 51044 Cov.: 31 AF XY: 0.812 AC XY: 60350 AN XY: 74356

African (AFR) AF: 0.910 AC: 37804 AN: 41546

American (AMR) AF: 0.805 AC: 12312 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4715 AN: 5178

South Asian (SAS) AF: 0.701 AC: 3371 AN: 4812

European-Finnish (FIN) AF: 0.734 AC: 7756 AN: 10566

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.774 AC: 52638 AN: 67976

Other (OTH) AF: 0.821 AC: 1730 AN: 2108

Alfa AF: 0.791 Hom.: 206998

Bravo AF: 0.830

Asia WGS AF: 0.747 AC: 2598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.64
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1229976; hg19: chr4-100202078;