Variant rs7041 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000583.4(GC):c.1296T>G(p.Asp432Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151994 control chromosomes in the gnomAD Genomes database, including 17953 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.45 ( 17953 hom., cov: 32)

Exomes 𝑓: 0.52 ( 36331 hom. )

Consequence

GC
NM_000583.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.89

Links

GC (HGNC:4187):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.460173E-6).

BP6

Variant 4-71752617-A-C is Benign according to our data. Variant chr4-71752617-A-C is described in ClinVar as [Benign]. Clinvar id is 15987. Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GC	NM_000583.4 linkuse as main transcript	c.1296T>G	p.Asp432Glu	missense_variant	11/13	ENST00000273951.13
GC	NM_001204307.1 linkuse as main transcript	c.1353T>G	p.Asp451Glu	missense_variant	12/14
GC	NM_001204306.1 linkuse as main transcript	c.1296T>G	p.Asp432Glu	missense_variant	12/14
GC	XM_006714177.3 linkuse as main transcript	c.1262+1794T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13 linkuse as main transcript	c.1296T>G	p.Asp432Glu	missense_variant	11/13	1	NM_000583.4	P1	P02774-1

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68273

AN:

151994

Hom.:

17953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.469

GnomAD3 exomes

AF:

0.522

AC:

131047

AN:

251206

Hom.:

36331

AF XY:

0.531

AC XY:

72119

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.508

Gnomad ASJ exome

AF:

0.598

Gnomad EAS exome

AF:

0.286

Gnomad SAS exome

AF:

0.551

Gnomad FIN exome

AF:

0.675

Gnomad NFE exome

AF:

0.571

Gnomad OTH exome

AF:

0.554

GnomAD4 exome

AF:

0.545

AC:

796152

AN:

1459866

Hom.:

222353

AF XY:

0.547

AC XY:

397490

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.511

Gnomad4 ASJ exome

AF:

0.599

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.549

Gnomad4 FIN exome

AF:

0.669

Gnomad4 NFE exome

AF:

0.562

Gnomad4 OTH exome

AF:

0.529

Alfa

AF:

0.538

Hom.:

52790

Bravo

AF:

0.420

TwinsUK

AF:

0.559

AC:

2073

ALSPAC

AF:

0.555

AC:

2140

ESP6500AA

AF:

0.174

AC:

765

ESP6500EA

AF:

0.559

AC:

4808

ExAC

AF:

0.516

AC:

62622

Asia WGS

AF:

0.413

AC:

1434

AN:

3478

EpiCase

AF:

0.556

EpiControl

AF:

0.566

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GC1/GC2 POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jun 01, 1992

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.0010

Dann

Benign

0.46

DEOGEN2

Benign

0.073

T;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.42

T;T;T

MetaRNN

Benign

0.0000045

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.76

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.36

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.040

MutPred

0.39

Gain of glycosylation at T434 (P = 0.0279);.;Gain of glycosylation at T434 (P = 0.0279);

MPC

0.048

ClinPred

0.039

GERP RS

-10

Varity_R

0.17

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over