Variant 17-29968791-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_198529.4(EFCAB5):c.191A>G(p.Glu64Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,480,542 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict 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 (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

EFCAB5
NM_198529.4 missense, splice_region

Scores

Splicing: ADA: 0.3912

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.05

Variant links:

Genes affected

EFCAB5 (HGNC:24801): (EF-hand calcium binding domain 5) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB5 links:

EFCAB5 (HGNC:):

EFCAB5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052396953).

BP6

Variant 17-29968791-A-G is Benign according to our data. Variant chr17-29968791-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040137.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB5	NM_198529.4 linkuse as main transcript	c.191A>G	p.Glu64Gly	missense_variant, splice_region_variant	4/23	ENST00000394835.8	NP_940931.3	A4FU69-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB5	ENST00000394835.8 linkuse as main transcript	c.191A>G	p.Glu64Gly	missense_variant, splice_region_variant	4/23	1	NM_198529.4	ENSP00000378312.3		A4FU69-1

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

281

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00632

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000513

AC:

AN:

117006

Hom.:

AF XY:

0.000320

AC XY:

AN XY:

62438

show subpopulations

Gnomad AFR exome

AF:

0.00659

Gnomad AMR exome

AF:

0.000341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000597

Gnomad OTH exome

AF:

0.000641

GnomAD4 exome

AF:

0.000242

AC:

321

AN:

1328268

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

156

AN XY:

649394

show subpopulations

Gnomad4 AFR exome

AF:

0.00701

Gnomad4 AMR exome

AF:

0.000480

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.000568

GnomAD4 genome

AF:

0.00188

AC:

286

AN:

152274

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00645

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000460

Hom.:

Bravo

AF:

0.00229

ESP6500AA

AF:

0.00550

AC:

ESP6500EA

AF:

0.000127

AC:

ExAC

AF:

0.000396

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EFCAB5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 18, 2021

This variant is classified as likely 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

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0049

.;.;T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.55

T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

.;.;L;.

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.9

D;N;N;.

REVEL

Benign

0.070

Sift

Uncertain

0.0090

D;D;D;.

Sift4G

Uncertain

0.026

D;D;T;.

Polyphen

0.98

.;.;D;.

Vest4

0.20, 0.17

MVP

0.46

MPC

0.11

ClinPred

0.030

GERP RS

5.1

Varity_R

0.15

gMVP

0.076

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.39

dbscSNV1_RF

Benign

0.63

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