Variant 4-99345006-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000669.5(ADH1C):c.423C>T(p.Phe141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,614,162 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 5 hom. )

Consequence

ADH1C
NM_000669.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0100

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 4-99345006-G-A is Benign according to our data. Variant chr4-99345006-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 730985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.01 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1C	NM_000669.5 linkuse as main transcript	c.423C>T	p.Phe141=	synonymous_variant	5/9	ENST00000515683.6	NP_000660.1
ADH1C	NR_133005.2 linkuse as main transcript	n.494C>T		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADH1C	ENST00000515683.6 linkuse as main transcript	c.423C>T	p.Phe141=	synonymous_variant	5/9	1	NM_000669.5	ENSP00000426083	P1
ADH1C	ENST00000510055.5 linkuse as main transcript	c.303C>T	p.Phe101=	synonymous_variant	6/7	3		ENSP00000478439
ADH1C	ENST00000511397.3 linkuse as main transcript	c.321C>T	p.Phe107=	synonymous_variant	4/5	3		ENSP00000478545
ADH1C	ENST00000505942.2 linkuse as main transcript	n.446C>T		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00266

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.00137

AC:

345

AN:

251372

Hom.:

AF XY:

0.00146

AC XY:

199

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00269

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00230

AC:

3367

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1593

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00285

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00145

AC:

221

AN:

152268

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00266

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00208

Hom.:

Bravo

AF:

0.00153

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 18, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	ADH1C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.6

DANN

Benign

0.54

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over