chr4-99315605-C-T

Position:

• chr4-99315605-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.567+293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 457,870 control chromosomes in the GnomAD database, including 152,756 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 0.81 (49742 hom., cov: 32)
  • Exomes 𝑓: 0.82 (103014 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.567+293G>A		intron_variant		ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.447+293G>A		intron_variant			NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.567+293G>A		intron_variant		1	NM_000668.6	ENSP00000306606.8

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122869 AN: 152042 Hom.: 49698 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.824

GnomAD4 exome AF: 0.819 AC: 250387 AN: 305710 Hom.: 103014 Cov.: 3 AF XY: 0.815 AC XY: 132985 AN XY: 163178

Gnomad4 AFR exome AF: 0.768

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.847

Gnomad4 EAS exome AF: 0.921

Gnomad4 SAS exome AF: 0.751

Gnomad4 FIN exome AF: 0.813

Gnomad4 NFE exome AF: 0.827

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.808 AC: 122966 AN: 152160 Hom.: 49742 Cov.: 32 AF XY: 0.805 AC XY: 59909 AN XY: 74378

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.820

Alfa AF: 0.825 Hom.: 20144

Bravo AF: 0.810

Asia WGS AF: 0.766 AC: 2662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.8
DANN	Benign	0.67

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: rs1693457; hg19: chr4-100236762;