4-99319764-G-T

Position:

• chr4-99319764-G-T

Variant summary

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

The NM_000668.6(ADH1B):​c.19-878C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 152,162 control chromosomes in the GnomAD database, including 82 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 0.027 (82 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487

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=-0.92).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0275 (4181/152162) while in subpopulation SAS AF= 0.0546 (263/4820). AF 95% confidence interval is 0.0491. There are 82 homozygotes in gnomad4. There are 2129 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 82 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.19-878C>A		intron_variant		ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.-102-878C>A		intron_variant			NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.19-878C>A		intron_variant		1	NM_000668.6	ENSP00000306606.8

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4177 AN: 152044 Hom.: 82 Cov.: 33

Gnomad AFR AF: 0.00611

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0249

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0275 AC: 4181 AN: 152162 Hom.: 82 Cov.: 33 AF XY: 0.0286 AC XY: 2129 AN XY: 74394

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.0426

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0546

Gnomad4 FIN AF: 0.0552

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0271 Hom.: 63

Bravo AF: 0.0267

Asia WGS AF: 0.0320 AC: 111 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.51

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: rs1235416; hg19: chr4-100240921;