4-99310185-G-A

Variant names:

• chr4-99310185-G-A
• rs10033960
• NM_000668.6:c.1103+580C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000668.6(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 NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875
• Publications: 3 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 -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.

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.1103+580C>T		intron	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.983+580C>T		intron	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.1103+580C>T		intron	N/A	ENSP00000306606.8
	ADH1B	ENST00000625860.2	TSL:1	c.983+580C>T		intron	N/A	ENSP00000486614.1
	ADH1B	ENST00000506651.5	TSL:2	c.983+580C>T		intron	N/A	ENSP00000425998.2

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

African (AFR) AF: 0.0999 AC: 4143 AN: 41470

American (AMR) AF: 0.197 AC: 3011 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4127 AN: 5170

South Asian (SAS) AF: 0.483 AC: 2326 AN: 4812

European-Finnish (FIN) AF: 0.215 AC: 2268 AN: 10528

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19882 AN: 67914

Other (OTH) AF: 0.251 AC: 529 AN: 2110

Alfa AF: 0.264 Hom.: 732

Bravo AF: 0.236

Asia WGS AF: 0.474 AC: 1644 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.51
PhyloP100		0.88
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: rs10033960; hg19: chr4-100231342;