4-99321650-ACC-ACCC

Variant names:

• chr4-99321650-A-AC
• rs3076071
• NM_000668.6:c.-320_-319insG

Variant summary

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

The NM_000668.6(ADH1B):​c.-320_-319insG 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 0.11 (645 hom., cov: 0)
• Consequence: ADH1B NM_000668.6 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 645 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000668.6. 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.-320_-319insG		upstream_gene	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.-562_-561insG		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.-320_-319insG		upstream_gene	N/A	ENSP00000306606.8
	ADH1B	ENST00000506651.5	TSL:2	c.-562_-561insG		upstream_gene	N/A	ENSP00000425998.2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 14515 AN: 133858 Hom.: 648 Cov.: 0

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0966

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.108 AC: 14510 AN: 133956 Hom.: 645 Cov.: 0 AF XY: 0.109 AC XY: 7040 AN XY: 64726

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

African (AFR) AF: 0.155 AC: 5691 AN: 36748

American (AMR) AF: 0.141 AC: 1819 AN: 12920

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 648 AN: 3116

East Asian (EAS) AF: 0.0403 AC: 200 AN: 4958

South Asian (SAS) AF: 0.0838 AC: 360 AN: 4296

European-Finnish (FIN) AF: 0.107 AC: 853 AN: 7942

Middle Eastern (MID) AF: 0.154 AC: 39 AN: 254

European-Non Finnish (NFE) AF: 0.0750 AC: 4575 AN: 61028

Other (OTH) AF: 0.131 AC: 245 AN: 1866

⚠️ 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: 0.0505 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;