rs1789877

Variant names:

• chr4-99304901-A-G
• rs1789877
• NM_000668.6:c.*2939T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000668.6(ADH1B):​c.*2939T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 152,250 control chromosomes in the GnomAD database, including 86 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 0.032 (86 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ADH1B NM_000668.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0316 (4807/152250) while in subpopulation SAS AF= 0.0547 (264/4824). AF 95% confidence interval is 0.0493. There are 86 homozygotes in gnomad4. There are 2433 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 86 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.*2939T>C		downstream_gene_variant		ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.*2939T>C		downstream_gene_variant			NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.*2939T>C		downstream_gene_variant		1	NM_000668.6	ENSP00000306606.8
ADH1B	ENST00000625860.2	c.*2939T>C		downstream_gene_variant		1		ENSP00000486614.1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4803 AN: 152132 Hom.: 86 Cov.: 31

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0330

Gnomad OTH AF: 0.0307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0316 AC: 4807 AN: 152250 Hom.: 86 Cov.: 31 AF XY: 0.0327 AC XY: 2433 AN XY: 74444

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.0330

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0339 Hom.: 16

Bravo AF: 0.0316

Asia WGS AF: 0.0320 AC: 110 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1789877; hg19: chr4-100226058;