rs6413413

Variant names:

• chr4-99318127-T-A
• rs6413413
• NM_000668.6:c.178A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99318127-T-A
• chr4-99318127-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000668.6(ADH1B):​c.178A>T​(p.Thr60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,613,824 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0071 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (79 hom.)
• Consequence: ADH1B NM_000668.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83
• Publications: 22 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034271777).
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.178A>T	p.Thr60Ser	missense	Exon 3 of 9	NP_000659.2
	ADH1B	NM_001286650.2		c.58A>T	p.Thr20Ser	missense	Exon 4 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.178A>T	p.Thr60Ser	missense	Exon 3 of 9	ENSP00000306606.8
	ADH1B	ENST00000625860.2	TSL:1	c.58A>T	p.Thr20Ser	missense	Exon 3 of 9	ENSP00000486614.1
	ADH1B	ENST00000881106.1		c.178A>T	p.Thr60Ser	missense	Exon 3 of 9	ENSP00000551165.1

Frequencies

GnomAD3 genomes AF: 0.00712 AC: 1081 AN: 151868 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000919

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00461

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00707

Gnomad OTH AF: 0.00672

GnomAD2 exomes AF: 0.00757 AC: 1902 AN: 251370 AF XY: 0.00764

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.00327

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0390

Gnomad NFE exome AF: 0.00700

Gnomad OTH exome AF: 0.00635

GnomAD4 exome AF: 0.00744 AC: 10882 AN: 1461838 Hom.: 79 Cov.: 38 AF XY: 0.00724 AC XY: 5265 AN XY: 727222

African (AFR) AF: 0.00146 AC: 49 AN: 33476

American (AMR) AF: 0.00313 AC: 140 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00291 AC: 76 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00189 AC: 163 AN: 86258

European-Finnish (FIN) AF: 0.0357 AC: 1908 AN: 53420

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5766

European-Non Finnish (NFE) AF: 0.00725 AC: 8061 AN: 1111972

Other (OTH) AF: 0.00684 AC: 413 AN: 60394

GnomAD4 genome AF: 0.00711 AC: 1081 AN: 151986 Hom.: 8 Cov.: 32 AF XY: 0.00883 AC XY: 656 AN XY: 74276

African (AFR) AF: 0.000916 AC: 38 AN: 41480

American (AMR) AF: 0.00460 AC: 70 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4814

European-Finnish (FIN) AF: 0.0437 AC: 462 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00708 AC: 481 AN: 67984

Other (OTH) AF: 0.00665 AC: 14 AN: 2106

Alfa AF: 0.00583 Hom.: 4

Bravo AF: 0.00415

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00558 AC: 48

ExAC AF: 0.00659 AC: 800

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00682

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0020
DANN	Benign	0.22
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.94	T
PhyloP100		-4.8
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.017
Sift	Benign	0.74	T
Sift4G	Benign	0.33	T
Vest4		0.060
MutPred		0.23		Loss of glycosylation at T60 (P = 0.0394)
MVP		0.13
MPC		0.15
ClinPred		0.0032	T
GERP RS		-8.8
gMVP		0.26
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6413413; hg19: chr4-100239284;