Variant 4-99420682-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000673.7(ADH7):c.676A>G(p.Lys226Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,613,840 control chromosomes in the GnomAD database, including 355 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 174 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 181 hom. )

Consequence

ADH7
NM_000673.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

ADH7 (HGNC:256): (alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide) This gene encodes class IV alcohol dehydrogenase 7 mu or sigma subunit, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The enzyme encoded by this gene is inefficient in ethanol oxidation, but is the most active as a retinol dehydrogenase; thus it may participate in the synthesis of retinoic acid, a hormone important for cellular differentiation. The expression of this gene is much more abundant in stomach than liver, thus differing from the other known gene family members. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ADH7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026580095).

BP6

Variant 4-99420682-T-C is Benign according to our data. Variant chr4-99420682-T-C is described in ClinVar as [Benign]. Clinvar id is 776001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH7	NM_000673.7 link	c.676A>G	p.Lys226Glu	missense_variant	6/9	ENST00000437033.7	NP_000664.3	P40394
ADH7	NM_001166504.2 link	c.736A>G	p.Lys246Glu	missense_variant	6/9		NP_001159976.1	P40394-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADH7	ENST00000437033.7 link	c.676A>G	p.Lys226Glu	missense_variant	6/9	1	NM_000673.7	ENSP00000414254.2	A0A0C4DG85
ADH7	ENST00000209665.8 link	c.712A>G	p.Lys238Glu	missense_variant	6/9	1		ENSP00000209665.4	P40394-1
ADH7	ENST00000476959.5 link	c.736A>G	p.Lys246Glu	missense_variant	6/9	2		ENSP00000420269.1	P40394-2
ADH7	ENST00000482593.5 link	c.505A>G	p.Lys169Glu	missense_variant	7/10	3		ENSP00000420613.1	E9PFG0

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3937

AN:

152050

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00884

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.00721

AC:

1811

AN:

251158

Hom.:

AF XY:

0.00537

AC XY:

729

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.0913

Gnomad AMR exome

AF:

0.00545

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000933

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00318

AC:

4644

AN:

1461672

Hom.:

181

Cov.:

AF XY:

0.00278

AC XY:

2025

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.0953

Gnomad4 AMR exome

AF:

0.00651

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000654

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.0258

AC:

3933

AN:

152168

Hom.:

174

Cov.:

AF XY:

0.0258

AC XY:

1922

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0890

Gnomad4 AMR

AF:

0.00883

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00486

Hom.:

Bravo

AF:

0.0299

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0858

AC:

378

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00868

AC:

1054

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.66

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

T;T;.;.

Eigen

Benign

0.033

Eigen_PC

Benign

0.066

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.79

T;T;T;T

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.98

L;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.079

Sift

Benign

0.40

T;T;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.95

P;.;.;.

Vest4

0.15

MVP

0.55

MPC

0.057

ClinPred

0.022

GERP RS

2.6

Varity_R

0.18

gMVP

0.37

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