rs1789882

Positions:

• chr4-99313896-A-C
• chr4-99313896-A-G
• chr4-99313896-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000668.6(ADH1B):​c.753T>G​(p.Ile251Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADH1B NM_000668.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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]

ADH1B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.753T>G	p.Ile251Met	missense_variant	6/9	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.633T>G	p.Ile211Met	missense_variant	7/10		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.753T>G	p.Ile251Met	missense_variant	6/9	1	NM_000668.6	ENSP00000306606.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1460928 Hom.: 0 Cov.: 95 AF XY: 0.00000138 AC XY: 1 AN XY: 726788

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0077	.;T;T;.
Eigen	Benign	0.0072
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.81	.;T;.;T
M_CAP	Benign	0.0083	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-1.2	T
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.8	D;.;.;.
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;.
Vest4		0.50
MutPred		0.73		Gain of disorder (P = 0.036);.;.;Gain of disorder (P = 0.036);
MVP		0.16
MPC		0.67
ClinPred		0.98	D
GERP RS		2.0
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1789882; hg19: chr4-100235053;