NM_000668.6:c.259+91T>G

Variant names:

• chr4-99317955-A-C
• rs4147536
• NM_000668.6:c.259+91T>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+91T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,564,178 control chromosomes in the GnomAD database, including 470,080 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 0.72 (40239 hom., cov: 32)
  • Exomes 𝑓: 0.78 (429841 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• Publications: 36 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 (EAS) allele frequency at 95% confidence interval = 0.891 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+91T>G		intron	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.139+91T>G		intron	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.259+91T>G		intron	N/A	ENSP00000306606.8	P00325-1
	ADH1B	ENST00000625860.2	TSL:1	c.139+91T>G		intron	N/A	ENSP00000486614.1	P00325-2
	ADH1B	ENST00000881106.1		c.259+91T>G		intron	N/A	ENSP00000551165.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109442 AN: 151954 Hom.: 40229 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.746

GnomAD4 exome AF: 0.778 AC: 1099060 AN: 1412106 Hom.: 429841 Cov.: 31 AF XY: 0.778 AC XY: 543532 AN XY: 698510

African (AFR) AF: 0.545 AC: 17218 AN: 31568

American (AMR) AF: 0.712 AC: 26184 AN: 36798

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 18324 AN: 22728

East Asian (EAS) AF: 0.921 AC: 36299 AN: 39428

South Asian (SAS) AF: 0.702 AC: 54172 AN: 77124

European-Finnish (FIN) AF: 0.745 AC: 38479 AN: 51678

Middle Eastern (MID) AF: 0.745 AC: 3006 AN: 4036

European-Non Finnish (NFE) AF: 0.789 AC: 860783 AN: 1090586

Other (OTH) AF: 0.767 AC: 44595 AN: 58160

GnomAD4 genome AF: 0.720 AC: 109494 AN: 152072 Hom.: 40239 Cov.: 32 AF XY: 0.718 AC XY: 53340 AN XY: 74300

African (AFR) AF: 0.558 AC: 23141 AN: 41462

American (AMR) AF: 0.743 AC: 11362 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2776 AN: 3472

East Asian (EAS) AF: 0.913 AC: 4715 AN: 5166

South Asian (SAS) AF: 0.708 AC: 3408 AN: 4814

European-Finnish (FIN) AF: 0.740 AC: 7811 AN: 10562

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53690 AN: 67994

Other (OTH) AF: 0.742 AC: 1568 AN: 2112

Alfa AF: 0.770 Hom.: 65649

Bravo AF: 0.714

Asia WGS AF: 0.717 AC: 2490 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	0.49
DANN	Benign	0.42
PhyloP100		-0.86
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: rs4147536; hg19: chr4-100239112;