Variant 4-99141668-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000670.5(ADH4):c.135T>C(p.Ser45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,613,892 control chromosomes in the GnomAD database, including 759,040 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 0.96 ( 70035 hom., cov: 32)

Exomes 𝑓: 0.97 ( 689005 hom. )

Consequence

ADH4
NM_000670.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.26

Variant links:

Genes affected

ADH4 (HGNC:252): (alcohol dehydrogenase 4 (class II), pi polypeptide) This gene encodes class II alcohol dehydrogenase 4 pi subunit, which 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. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]

ADH4 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-4.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADH4	NM_000670.5 linkuse as main transcript	c.135T>C	p.Ser45=	synonymous_variant	3/9	ENST00000265512.12	NP_000661.2
LOC100507053	NR_037884.1 linkuse as main transcript	n.679+7863A>G		intron_variant, non_coding_transcript_variant
ADH4	NM_001306171.2 linkuse as main transcript	c.192T>C	p.Ser64=	synonymous_variant	4/10		NP_001293100.1
ADH4	NM_001306172.2 linkuse as main transcript	c.192T>C	p.Ser64=	synonymous_variant	4/10		NP_001293101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12 linkuse as main transcript	c.135T>C	p.Ser45=	synonymous_variant	3/9	1	NM_000670.5	ENSP00000265512	P1	P08319-1
	ENST00000500358.6 linkuse as main transcript	n.679+7863A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.959

AC:

145895

AN:

152118

Hom.:

69985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.934

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.957

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.979

Gnomad FIN

AF:

0.945

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.971

Gnomad OTH

AF:

0.968

GnomAD3 exomes

AF:

0.965

AC:

242326

AN:

251158

Hom.:

116977

AF XY:

0.969

AC XY:

131465

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.931

Gnomad AMR exome

AF:

0.933

Gnomad ASJ exome

AF:

0.980

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.982

Gnomad FIN exome

AF:

0.942

Gnomad NFE exome

AF:

0.972

Gnomad OTH exome

AF:

0.965

GnomAD4 exome

AF:

0.971

AC:

1419026

AN:

1461656

Hom.:

689005

Cov.:

AF XY:

0.972

AC XY:

706435

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.931

Gnomad4 AMR exome

AF:

0.934

Gnomad4 ASJ exome

AF:

0.978

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.982

Gnomad4 FIN exome

AF:

0.941

Gnomad4 NFE exome

AF:

0.973

Gnomad4 OTH exome

AF:

0.972

GnomAD4 genome

AF:

0.959

AC:

146004

AN:

152236

Hom.:

70035

Cov.:

AF XY:

0.959

AC XY:

71405

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.934

Gnomad4 AMR

AF:

0.957

Gnomad4 ASJ

AF:

0.973

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.979

Gnomad4 FIN

AF:

0.945

Gnomad4 NFE

AF:

0.971

Gnomad4 OTH

AF:

0.968

Alfa

AF:

0.969

Hom.:

124763

Bravo

AF:

0.957

Asia WGS

AF:

0.977

AC:

3399

AN:

3478

EpiCase

AF:

0.977

EpiControl

AF:

0.975

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

DANN

Benign

0.49

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over