rs1229984

chr4-99318162-T-Achr4-99318162-T-Cchr4-99318162-T-G

Variant summary

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

The NM_000668.6(ADH1B):c.143A>T(p.His48Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H48R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADH1B NM_000668.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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 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	UniProt
ADH1B	NM_000668.6	c.143A>T	p.His48Leu	missense_variant	3/9	ENST00000305046.13
ADH1B	NM_001286650.2	c.23A>T	p.His8Leu	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1B	ENST00000305046.13	c.143A>T	p.His48Leu	missense_variant	3/9	1	NM_000668.6	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	20
Dann	Benign	0.95
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.0058	T
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.97	D;D
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.5	D;.;.;.
REVEL	Benign	0.10
Sift	Benign	0.037	D;.;.;.
Sift4G	Uncertain	0.0060	D;D;D;.
Vest4		0.28
MutPred		0.76		.;Loss of disorder (P = 0.005);Loss of disorder (P = 0.005);.;
MVP		0.28
MPC		0.22
ClinPred		0.88	D
GERP RS		3.6
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-100239319;