rs4147539

Variant names:

• chr4-99316322-GTTC-G
• rs4147539
• NM_000668.6:c.260-23_260-21delGAA

Your query was ambiguous. Multiple possible variants found:

• chr4-99316322-GTTC-G
• chr4-99316322-GTTC-GTTCTTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000668.6(ADH1B):​c.260-23_260-21delGAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 1,605,764 control chromosomes in the GnomAD database, including 8,919 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.096 (1008 hom., cov: 31)
  • Exomes 𝑓: 0.090 (7911 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 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.260-23_260-21delGAA		intron	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.140-23_140-21delGAA		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.260-23_260-21delGAA		intron	N/A	ENSP00000306606.8	P00325-1
	ADH1B	ENST00000625860.2	TSL:1	c.140-23_140-21delGAA		intron	N/A	ENSP00000486614.1	P00325-2
	ADH1B	ENST00000881106.1		c.260-23_260-21delGAA		intron	N/A	ENSP00000551165.1

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14529 AN: 152130 Hom.: 1001 Cov.: 31

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0966

GnomAD2 exomes AF: 0.119 AC: 29615 AN: 249342 AF XY: 0.107

Gnomad AFR exome AF: 0.0666

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.0893

Gnomad EAS exome AF: 0.0763

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0831

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0900 AC: 130748 AN: 1453516 Hom.: 7911 AF XY: 0.0876 AC XY: 63386 AN XY: 723572

African (AFR) AF: 0.0670 AC: 2228 AN: 33238

American (AMR) AF: 0.342 AC: 15215 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 2212 AN: 26070

East Asian (EAS) AF: 0.0760 AC: 3014 AN: 39648

South Asian (SAS) AF: 0.0476 AC: 4091 AN: 86006

European-Finnish (FIN) AF: 0.126 AC: 6740 AN: 53384

Middle Eastern (MID) AF: 0.0756 AC: 434 AN: 5740

European-Non Finnish (NFE) AF: 0.0830 AC: 91667 AN: 1104822

Other (OTH) AF: 0.0856 AC: 5147 AN: 60094

GnomAD4 genome AF: 0.0956 AC: 14553 AN: 152248 Hom.: 1008 Cov.: 31 AF XY: 0.100 AC XY: 7478 AN XY: 74440

African (AFR) AF: 0.0678 AC: 2818 AN: 41556

American (AMR) AF: 0.235 AC: 3589 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.0878 AC: 455 AN: 5184

South Asian (SAS) AF: 0.0591 AC: 285 AN: 4822

European-Finnish (FIN) AF: 0.134 AC: 1418 AN: 10598

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0800 AC: 5442 AN: 68018

Other (OTH) AF: 0.0979 AC: 207 AN: 2114

Alfa AF: 0.0843 Hom.: 131

Bravo AF: 0.106

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45
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: rs4147539; hg19: chr4-100237479;