chr4-99307309-T-C

Variant names:

• chr4-99307309-T-C
• rs1042026
• NM_000668.6:c.*531A>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.*531A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 155,136 control chromosomes in the GnomAD database, including 6,284 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 (6167 hom., cov: 32)
  • Exomes 𝑓: 0.23 (117 hom.)
• Consequence: ADH1B NM_000668.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 68 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 = 0.779 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.*531A>G		3_prime_UTR	Exon 9 of 9	NP_000659.2
	ADH1B	NM_001286650.2		c.*531A>G		3_prime_UTR	Exon 10 of 10	NP_001273579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.*531A>G		3_prime_UTR	Exon 9 of 9	ENSP00000306606.8
	ADH1B	ENST00000625860.2	TSL:1	c.*531A>G		3_prime_UTR	Exon 9 of 9	ENSP00000486614.1
	ADH1B	ENST00000515694.4	TSL:2	n.3754A>G		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37856 AN: 152060 Hom.: 6176 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.235 AC: 695 AN: 2958 Hom.: 117 Cov.: 0 AF XY: 0.253 AC XY: 364 AN XY: 1438

African (AFR) AF: 0.0769 AC: 2 AN: 26

American (AMR) AF: 0.226 AC: 14 AN: 62

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 8 AN: 64

East Asian (EAS) AF: 1.00 AC: 18 AN: 18

South Asian (SAS) AF: 0.374 AC: 68 AN: 182

European-Finnish (FIN) AF: 0.201 AC: 29 AN: 144

Middle Eastern (MID) AF: 0.313 AC: 5 AN: 16

European-Non Finnish (NFE) AF: 0.227 AC: 504 AN: 2224

Other (OTH) AF: 0.212 AC: 47 AN: 222

GnomAD4 genome AF: 0.249 AC: 37836 AN: 152178 Hom.: 6167 Cov.: 32 AF XY: 0.252 AC XY: 18731 AN XY: 74420

African (AFR) AF: 0.101 AC: 4217 AN: 41552

American (AMR) AF: 0.201 AC: 3078 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 869 AN: 3464

East Asian (EAS) AF: 0.799 AC: 4138 AN: 5176

South Asian (SAS) AF: 0.483 AC: 2327 AN: 4818

European-Finnish (FIN) AF: 0.215 AC: 2271 AN: 10584

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19977 AN: 67984

Other (OTH) AF: 0.255 AC: 540 AN: 2114

Alfa AF: 0.291 Hom.: 22750

Bravo AF: 0.238

Asia WGS AF: 0.476 AC: 1651 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	2.6
DANN	Benign	0.58
PhyloP100		0.024
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: rs1042026; hg19: chr4-100228466;