Variant chr4-99342788-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000669.5(ADH1C):c.828+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,610,326 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 14 hom. )

Consequence

ADH1C
NM_000669.5 splice_region, intron

Scores

Splicing: ADA: 0.00001002

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.185

Variant links:

Genes affected

ADH1C (HGNC:251): (alcohol dehydrogenase 1C (class I), gamma polypeptide) This gene encodes class I alcohol dehydrogenase, gamma 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 I alcohol dehydrogenase, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation to acetaldehyde, thus playing 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. An association between ADH1C polymorphism and alcohol dependence has not been established. [provided by RefSeq, Sep 2019]

ADH1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-99342788-A-T is Benign according to our data. Variant chr4-99342788-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654964.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1C	NM_000669.5 linkuse as main transcript	c.828+7T>A		splice_region_variant, intron_variant		ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 linkuse as main transcript	n.855+51T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1C	ENST00000515683.6 linkuse as main transcript	c.828+7T>A		splice_region_variant, intron_variant		1	NM_000669.5	ENSP00000426083	P1

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

434

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00500

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00169

AC:

424

AN:

250476

Hom.:

AF XY:

0.00172

AC XY:

233

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00339

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00251

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00282

AC:

4111

AN:

1457966

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

1983

AN XY:

725396

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00453

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00110

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00327

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.00285

AC:

434

AN:

152360

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00498

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00441

Hom.:

Bravo

AF:

0.00278

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

ADH1C: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.45

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000010

dbscSNV1_RF

Benign

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over