rs1693457

Variant names:

• chr4-99315605-C-A
• rs1693457
• NM_000668.6:c.567+293G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99315605-C-A
• chr4-99315605-C-G
• chr4-99315605-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000668.6(ADH1B):​c.567+293G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 24 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.567+293G>T		intron_variant	Intron 5 of 8	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.447+293G>T		intron_variant	Intron 6 of 9		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.567+293G>T		intron_variant	Intron 5 of 8	1	NM_000668.6	ENSP00000306606.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 306130 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 163404

African (AFR) AF: 0.00 AC: 0 AN: 9030

American (AMR) AF: 0.00 AC: 0 AN: 12586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9064

East Asian (EAS) AF: 0.00 AC: 0 AN: 17646

South Asian (SAS) AF: 0.00 AC: 0 AN: 40508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 183016

Other (OTH) AF: 0.00 AC: 0 AN: 17048

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.61
PhyloP100		0.080

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: rs1693457; hg19: chr4-100236762;