rs10033960

Positions:

• chr4-99310185-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000305046.13(ADH1B):​c.1103+580C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,934 control chromosomes in the GnomAD database, including 6,099 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 0.25 (6099 hom., cov: 32)
• Consequence: ADH1B ENST00000305046.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.1103+580C>T		intron_variant		ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.983+580C>T		intron_variant			NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.1103+580C>T		intron_variant		1	NM_000668.6	ENSP00000306606	P1
ADH1B	ENST00000625860.2	c.983+580C>T		intron_variant		1		ENSP00000486614
ADH1B	ENST00000506651.5	c.983+580C>T		intron_variant		2		ENSP00000425998
ADH1B	ENST00000515694.4	n.3198+580C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37582 AN: 151814 Hom.: 6108 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.247 AC: 37563 AN: 151934 Hom.: 6099 Cov.: 32 AF XY: 0.250 AC XY: 18576 AN XY: 74248

Gnomad4 AFR AF: 0.0999

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.251

Alfa AF: 0.270 Hom.: 730

Bravo AF: 0.236

Asia WGS AF: 0.474 AC: 1644 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs10033960; hg19: chr4-100231342;