rs1353621

Positions:

• chr4-99320418-T-C
• chr4-99320418-T-G

Variant summary

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

The ENST00000305046.13(ADH1B):​c.18+896A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,556 control chromosomes in the GnomAD database, including 6,959 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 0.27 (6922 hom., cov: 32)
  • Exomes 𝑓: 0.31 (37 hom.)
• Consequence: ADH1B ENST00000305046.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.18+896A>G		intron_variant		ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.-103+375A>G		intron_variant			NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.18+896A>G		intron_variant		1	NM_000668.6	ENSP00000306606	P1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41310 AN: 151892 Hom.: 6926 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.313 AC: 171 AN: 546 Hom.: 37 Cov.: 0 AF XY: 0.293 AC XY: 95 AN XY: 324

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.306

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.272 AC: 41311 AN: 152010 Hom.: 6922 Cov.: 32 AF XY: 0.266 AC XY: 19735 AN XY: 74266

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.317

Alfa AF: 0.354 Hom.: 12801

Bravo AF: 0.258

Asia WGS AF: 0.0990 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.76

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: rs1353621; hg19: chr4-100241575; COSMIC: COSV59298941; COSMIC: COSV59298941;