chr4-99317841-T-C

Variant names:

• chr4-99317841-T-C
• rs2075633
• NM_000668.6:c.259+205A>G

Variant summary

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

The NM_000668.6(ADH1B):​c.259+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 731,672 control chromosomes in the GnomAD database, including 41,932 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 0.25 (6155 hom., cov: 32)
  • Exomes 𝑓: 0.32 (35777 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.259+205A>G		intron	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.139+205A>G		intron	N/A	NP_001273579.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.259+205A>G		intron	N/A	ENSP00000306606.8
	ADH1B	ENST00000625860.2	TSL:1	c.139+205A>G		intron	N/A	ENSP00000486614.1
	ADH1B	ENST00000881106.1		c.259+205A>G		intron	N/A	ENSP00000551165.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37784 AN: 151954 Hom.: 6164 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.321 AC: 186184 AN: 579600 Hom.: 35777 Cov.: 8 AF XY: 0.329 AC XY: 98451 AN XY: 299210

African (AFR) AF: 0.0996 AC: 1457 AN: 14632

American (AMR) AF: 0.164 AC: 2548 AN: 15532

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 3498 AN: 14114

East Asian (EAS) AF: 0.830 AC: 25456 AN: 30674

South Asian (SAS) AF: 0.458 AC: 19761 AN: 43136

European-Finnish (FIN) AF: 0.224 AC: 7555 AN: 33720

Middle Eastern (MID) AF: 0.287 AC: 637 AN: 2220

European-Non Finnish (NFE) AF: 0.294 AC: 116221 AN: 395632

Other (OTH) AF: 0.302 AC: 9051 AN: 29940

GnomAD4 genome AF: 0.248 AC: 37766 AN: 152072 Hom.: 6155 Cov.: 32 AF XY: 0.252 AC XY: 18712 AN XY: 74350

African (AFR) AF: 0.102 AC: 4217 AN: 41502

American (AMR) AF: 0.202 AC: 3080 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4139 AN: 5164

South Asian (SAS) AF: 0.483 AC: 2325 AN: 4814

European-Finnish (FIN) AF: 0.216 AC: 2281 AN: 10580

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19896 AN: 67952

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.279 Hom.: 20389

Bravo AF: 0.237

Asia WGS AF: 0.477 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2075633; hg19: chr4-100238998;