Variant chr4-99282290-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000667.4(ADH1A):c.828+56T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 1,613,972 control chromosomes in the GnomAD database, including 9,161 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 0.092 ( 983 hom., cov: 32)

Exomes 𝑓: 0.091 ( 8178 hom. )

Consequence

ADH1A
NM_000667.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.251

Variant links:

Genes affected

ADH1A (HGNC:249): (alcohol dehydrogenase 1A (class I), alpha polypeptide) This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence. [provided by RefSeq, Nov 2010]

ADH1A links:

ADH1A (HGNC:):

ADH1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1A	NM_000667.4 linkuse as main transcript	c.828+56T>G		intron_variant		ENST00000209668.3	NP_000658.1	P07327
LOC100507053	NR_037884.1 linkuse as main transcript	n.3790-4505A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3 linkuse as main transcript	c.828+56T>G		intron_variant		1	NM_000667.4	ENSP00000209668.2		P07327

Frequencies

GnomAD3 genomes

AF:

0.0924

AC:

14051

AN:

152140

Hom.:

978

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0556

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.0832

Gnomad EAS

AF:

0.0894

Gnomad SAS

AF:

0.0590

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0805

Gnomad OTH

AF:

0.0917

GnomAD3 exomes

AF:

0.120

AC:

29926

AN:

250290

Hom.:

3253

AF XY:

0.108

AC XY:

14622

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.0560

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.0876

Gnomad EAS exome

AF:

0.0805

Gnomad SAS exome

AF:

0.0457

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0847

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0912

AC:

133255

AN:

1461714

Hom.:

8178

Cov.:

AF XY:

0.0889

AC XY:

64654

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.0561

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.0829

Gnomad4 EAS exome

AF:

0.0775

Gnomad4 SAS exome

AF:

0.0481

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.0848

Gnomad4 OTH exome

AF:

0.0848

GnomAD4 genome

AF:

0.0924

AC:

14073

AN:

152258

Hom.:

983

Cov.:

AF XY:

0.0969

AC XY:

7215

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0554

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.0832

Gnomad4 EAS

AF:

0.0893

Gnomad4 SAS

AF:

0.0599

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.0806

Gnomad4 OTH

AF:

0.0926

Alfa

AF:

0.0879

Hom.:

720

Bravo

AF:

0.102

Asia WGS

AF:

0.118

AC:

411

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.4

DANN

Benign

0.56

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