rs6850217

Positions:

• chr4-99312463-C-T

Variant summary

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

The NM_000668.6(ADH1B):​c.829-807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,036 control chromosomes in the GnomAD database, including 7,338 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 0.29 (7338 hom., cov: 32)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1B	NM_000668.6	c.829-807G>A		intron_variant		ENST00000305046.13
ADH1B	NM_001286650.2	c.709-807G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13	c.829-807G>A		intron_variant		1	NM_000668.6	P1
ADH1B	ENST00000625860.2	c.709-807G>A		intron_variant		1
ADH1B	ENST00000506651.5	c.709-807G>A		intron_variant		2
ADH1B	ENST00000515694.4	n.2924-807G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43780 AN: 151918 Hom.: 7338 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.0251

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.288 AC: 43791 AN: 152036 Hom.: 7338 Cov.: 32 AF XY: 0.281 AC XY: 20868 AN XY: 74290

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.330

Alfa AF: 0.332 Hom.: 1005

Bravo AF: 0.276

Asia WGS AF: 0.103 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.15
DANN	Benign	0.37

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: rs6850217; hg19: chr4-100233620;