rs1789877

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 86 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000668.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.*2939T>C		downstream_gene	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.*2939T>C		downstream_gene	N/A	NP_001273579.1	D6RHZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.*2939T>C		downstream_gene	N/A	ENSP00000306606.8	P00325-1
	ADH1B	ENST00000625860.2	TSL:1	c.*2939T>C		downstream_gene	N/A	ENSP00000486614.1	P00325-2

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

African (AFR) AF: 0.0187 AC: 778 AN: 41564

American (AMR) AF: 0.0465 AC: 712 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3464

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0547 AC: 264 AN: 4824

European-Finnish (FIN) AF: 0.0548 AC: 581 AN: 10596

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0330 AC: 2243 AN: 68010

Other (OTH) AF: 0.0308 AC: 65 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.58
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs1789877; hg19: chr4-100226058;