rs28626993

Variant names:

• chr4-99314037-G-A
• rs28626993
• NM_000668.6:c.612C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99314037-G-A
• chr4-99314037-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000668.6(ADH1B):​c.612C>T​(p.Val204Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,614,150 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (117 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (107 hom.)
• Consequence: ADH1B NM_000668.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15
• Publications: 5 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 4-99314037-G-A is Benign according to our data. Variant chr4-99314037-G-A is described in ClinVar as [Benign]. Clinvar id is 772869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.612C>T	p.Val204Val	synonymous_variant	Exon 6 of 9	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.492C>T	p.Val164Val	synonymous_variant	Exon 7 of 10		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.612C>T	p.Val204Val	synonymous_variant	Exon 6 of 9	1	NM_000668.6	ENSP00000306606.8

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 3061 AN: 152142 Hom.: 117 Cov.: 33

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00490 AC: 1233 AN: 251436 AF XY: 0.00347

Gnomad AFR exome AF: 0.0706

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00200 AC: 2926 AN: 1461890 Hom.: 107 Cov.: 33 AF XY: 0.00170 AC XY: 1233 AN XY: 727244

African (AFR) AF: 0.0750 AC: 2510 AN: 33480

American (AMR) AF: 0.00208 AC: 93 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0000638 AC: 71 AN: 1112008

Other (OTH) AF: 0.00389 AC: 235 AN: 60396

GnomAD4 genome AF: 0.0201 AC: 3067 AN: 152260 Hom.: 117 Cov.: 33 AF XY: 0.0195 AC XY: 1455 AN XY: 74448

African (AFR) AF: 0.0712 AC: 2958 AN: 41524

American (AMR) AF: 0.00431 AC: 66 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68020

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.00725 Hom.: 14

Bravo AF: 0.0224

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.59
DANN	Benign	0.57
PhyloP100		-1.1
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: rs28626993; hg19: chr4-100235194; COSMIC: COSV104615188; COSMIC: COSV104615188;