4-99277355-A-T

Variant names:

• chr4-99277355-A-T
• rs2866151
• NM_000667.4:c.1104-707T>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.1104-707T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,912 control chromosomes in the GnomAD database, including 12,611 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 0.39 (12611 hom., cov: 32)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 15 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 (AMR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1A	NM_000667.4	c.1104-707T>A		intron_variant	Intron 8 of 8	ENST00000209668.3	NP_000658.1
LOC100507053	NR_037884.1	n.3790-9440A>T		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3	c.1104-707T>A		intron_variant	Intron 8 of 8	1	NM_000667.4	ENSP00000209668.2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59099 AN: 151794 Hom.: 12610 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.389 AC: 59132 AN: 151912 Hom.: 12611 Cov.: 32 AF XY: 0.386 AC XY: 28623 AN XY: 74244

African (AFR) AF: 0.232 AC: 9633 AN: 41468

American (AMR) AF: 0.508 AC: 7736 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1893 AN: 3472

East Asian (EAS) AF: 0.115 AC: 597 AN: 5176

South Asian (SAS) AF: 0.217 AC: 1047 AN: 4830

European-Finnish (FIN) AF: 0.480 AC: 5056 AN: 10532

Middle Eastern (MID) AF: 0.392 AC: 113 AN: 288

European-Non Finnish (NFE) AF: 0.467 AC: 31677 AN: 67890

Other (OTH) AF: 0.437 AC: 922 AN: 2112

Alfa AF: 0.414 Hom.: 1626

Bravo AF: 0.388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.5
DANN	Benign	0.32
PhyloP100		0.19
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: rs2866151; hg19: chr4-100198512;