4-99321650-ACC-AC

Variant names:

• chr4-99321650-AC-A
• rs3076071
• NM_000668.6:c.-320delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000305046.13(ADH1B):​c.-320delG variant causes a upstream gene 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 0.48 (16391 hom., cov: 0)
• Consequence: ADH1B ENST00000305046.13 upstream_gene
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000305046.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.-320delG		upstream_gene	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.-562delG		upstream_gene	N/A	NP_001273579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.-320delG		upstream_gene	N/A	ENSP00000306606.8
	ADH1B	ENST00000506651.5	TSL:2	c.-562delG		upstream_gene	N/A	ENSP00000425998.2

Frequencies

GnomAD3 genomes AF: 0.481 AC: 65790 AN: 136714 Hom.: 16366 Cov.: 0

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.481 AC: 65866 AN: 136820 Hom.: 16391 Cov.: 0 AF XY: 0.487 AC XY: 32167 AN XY: 66086

African (AFR) AF: 0.617 AC: 23456 AN: 37994

American (AMR) AF: 0.477 AC: 6352 AN: 13308

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1139 AN: 3230

East Asian (EAS) AF: 0.894 AC: 4467 AN: 4998

South Asian (SAS) AF: 0.576 AC: 2511 AN: 4360

European-Finnish (FIN) AF: 0.347 AC: 2793 AN: 8040

Middle Eastern (MID) AF: 0.398 AC: 105 AN: 264

European-Non Finnish (NFE) AF: 0.385 AC: 23850 AN: 61886

Other (OTH) AF: 0.452 AC: 860 AN: 1904

Alfa AF: 0.211 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

Other links and lift over

dbSNP: rs3076071; hg19: chr4-100242807;