Variant 17-47374528-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000331493.7(EFCAB13):c.934G>A(p.Val312Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,572,736 control chromosomes in the GnomAD database, including 295,789 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.64 ( 31456 hom., cov: 32)

Exomes 𝑓: 0.61 ( 264333 hom. )

Consequence

EFCAB13
ENST00000331493.7 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.58

Variant links:

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

EFCAB13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.739846E-6).

BP6

Variant 17-47374528-G-A is Benign according to our data. Variant chr17-47374528-G-A is described in ClinVar as [Benign]. Clinvar id is 3059444.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB13	NM_152347.5 linkuse as main transcript	c.934G>A	p.Val312Ile	missense_variant	12/25	ENST00000331493.7	NP_689560.3
EFCAB13	NM_001195192.2 linkuse as main transcript	c.646G>A	p.Val216Ile	missense_variant	10/22		NP_001182121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7 linkuse as main transcript	c.934G>A	p.Val312Ile	missense_variant	12/25	1	NM_152347.5	ENSP00000332111	A2	Q8IY85-1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96932

AN:

151914

Hom.:

31406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.677

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.653

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.643

GnomAD3 exomes

AF:

0.596

AC:

128689

AN:

215798

Hom.:

38831

AF XY:

0.597

AC XY:

70157

AN XY:

117572

show subpopulations

Gnomad AFR exome

AF:

0.736

Gnomad AMR exome

AF:

0.495

Gnomad ASJ exome

AF:

0.642

Gnomad EAS exome

AF:

0.601

Gnomad SAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.540

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.598

GnomAD4 exome

AF:

0.609

AC:

864756

AN:

1420704

Hom.:

264333

Cov.:

AF XY:

0.608

AC XY:

429522

AN XY:

706142

show subpopulations

Gnomad4 AFR exome

AF:

0.733

Gnomad4 AMR exome

AF:

0.505

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.612

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.547

Gnomad4 NFE exome

AF:

0.612

Gnomad4 OTH exome

AF:

0.619

GnomAD4 genome

AF:

0.638

AC:

97049

AN:

152032

Hom.:

31456

Cov.:

AF XY:

0.631

AC XY:

46930

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.732

Gnomad4 AMR

AF:

0.575

Gnomad4 ASJ

AF:

0.678

Gnomad4 EAS

AF:

0.602

Gnomad4 SAS

AF:

0.558

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.616

Gnomad4 OTH

AF:

0.641

Alfa

AF:

0.616

Hom.:

70143

Bravo

AF:

0.644

TwinsUK

AF:

0.613

AC:

2272

ALSPAC

AF:

0.619

AC:

2384

ESP6500AA

AF:

0.724

AC:

3176

ESP6500EA

AF:

0.613

AC:

5226

ExAC

AF:

0.597

AC:

72341

Asia WGS

AF:

0.526

AC:

1828

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EFCAB13-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0020

DANN

Benign

0.17

DEOGEN2

Benign

0.00083

.;T;.

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.00099

LIST_S2

Benign

0.28

T;T;T

MetaRNN

Benign

0.0000017

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.010

.;N;N

REVEL

Benign

0.030

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.015, 0.050

MPC

0.11

ClinPred

0.0037

GERP RS

-8.0

Varity_R

0.021

gMVP

0.022

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