4-99321650-ACC-ACCCC

Variant names:

• chr4-99321650-A-ACC
• rs3076071
• ENST00000881097.1:c.-321_-320dupGG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000881097.1(ADH1B):​c.-321_-320dupGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0077 (10 hom., cov: 0)
• Consequence: ADH1B ENST00000881097.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874
• Publications: 1 publications found

Genes affected

ADH1B (HGNC:250): (alcohol dehydrogenase 1B (class I), beta polypeptide) The protein encoded by this gene is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This encoded protein, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000881097.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.-320_-319insGG		upstream_gene	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.-562_-561insGG		upstream_gene	N/A	NP_001273579.1	D6RHZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000881097.1		c.-321_-320dupGG		5_prime_UTR	Exon 1 of 9	ENSP00000551156.1
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.-321_-320dupGG		upstream_gene	N/A	ENSP00000306606.8	P00325-1
	ADH1B	ENST00000881106.1		c.-321_-320dupGG		upstream_gene	N/A	ENSP00000551165.1

Frequencies

GnomAD3 genomes AF: 0.00769 AC: 1045 AN: 135950 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0169

Gnomad AMR AF: 0.00605

Gnomad ASJ AF: 0.00248

Gnomad EAS AF: 0.000799

Gnomad SAS AF: 0.00115

Gnomad FIN AF: 0.00448

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00806

Gnomad OTH AF: 0.00532

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

GnomAD4 genome AF: 0.00768 AC: 1045 AN: 136052 Hom.: 10 Cov.: 0 AF XY: 0.00739 AC XY: 486 AN XY: 65728

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0104 AC: 393 AN: 37676

American (AMR) AF: 0.00596 AC: 79 AN: 13246

Ashkenazi Jewish (ASJ) AF: 0.00248 AC: 8 AN: 3222

East Asian (EAS) AF: 0.000801 AC: 4 AN: 4994

South Asian (SAS) AF: 0.00115 AC: 5 AN: 4348

European-Finnish (FIN) AF: 0.00448 AC: 36 AN: 8030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00806 AC: 496 AN: 61550

Other (OTH) AF: 0.00528 AC: 10 AN: 1894

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00886 Hom.: 298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3076071;

hg19: chr4-100242807;