4-99312463-C-T

Variant names:

• chr4-99312463-C-T
• rs6850217
• NM_000668.6:c.829-807G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000668.6(ADH1B):​c.829-807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,036 control chromosomes in the GnomAD database, including 7,338 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 0.29 (7338 hom., cov: 32)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.829-807G>A		intron	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.709-807G>A		intron	N/A	NP_001273579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.829-807G>A		intron	N/A	ENSP00000306606.8
	ADH1B	ENST00000625860.2	TSL:1	c.709-807G>A		intron	N/A	ENSP00000486614.1
	ADH1B	ENST00000506651.5	TSL:2	c.709-807G>A		intron	N/A	ENSP00000425998.2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43780 AN: 151918 Hom.: 7338 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.0251

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.288 AC: 43791 AN: 152036 Hom.: 7338 Cov.: 32 AF XY: 0.281 AC XY: 20868 AN XY: 74290

African (AFR) AF: 0.149 AC: 6169 AN: 41486

American (AMR) AF: 0.268 AC: 4089 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3472

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5172

South Asian (SAS) AF: 0.150 AC: 725 AN: 4820

European-Finnish (FIN) AF: 0.359 AC: 3781 AN: 10544

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26090 AN: 67952

Other (OTH) AF: 0.330 AC: 698 AN: 2114

Alfa AF: 0.332 Hom.: 1005

Bravo AF: 0.276

Asia WGS AF: 0.103 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.15
DANN	Benign	0.37
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs6850217; hg19: chr4-100233620;