Variant 17-47347814-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000331493.7(EFCAB13):c.524A>G(p.His175Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,496,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H175H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

EFCAB13
ENST00000331493.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.180

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026103526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB13	NM_152347.5 linkuse as main transcript	c.524A>G	p.His175Arg	missense_variant	9/25	ENST00000331493.7	NP_689560.3
EFCAB13	NM_001195192.2 linkuse as main transcript	c.517+2716A>G		intron_variant			NP_001182121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7 linkuse as main transcript	c.524A>G	p.His175Arg	missense_variant	9/25	1	NM_152347.5	ENSP00000332111	A2	Q8IY85-1
EFCAB13	ENST00000517310.5 linkuse as main transcript	c.73+2716A>G		intron_variant		2		ENSP00000466136
EFCAB13	ENST00000517484.5 linkuse as main transcript	c.517+2716A>G		intron_variant		2		ENSP00000430048	P2	Q8IY85-2
EFCAB13	ENST00000520776.5 linkuse as main transcript	n.651+2716A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000181

AC:

AN:

232236

Hom.:

AF XY:

0.000223

AC XY:

AN XY:

125818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000691

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000331

Gnomad OTH exome

AF:

0.000719

GnomAD4 exome

AF:

0.000156

AC:

210

AN:

1344610

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

658532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000404

Gnomad4 NFE exome

AF:

0.000186

Gnomad4 OTH exome

AF:

0.000128

GnomAD4 genome

AF:

0.000171

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.000206

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.524A>G (p.H175R) alteration is located in exon 9 (coding exon 6) of the EFCAB13 gene. This alteration results from a A to G substitution at nucleotide position 524, causing the histidine (H) at amino acid position 175 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.00067

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.40

M_CAP

Benign

0.0034

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.38

REVEL

Benign

0.029

Sift

Benign

0.048

Sift4G

Benign

0.53

Polyphen

0.22

Vest4

0.15

MVP

0.014

MPC

0.24

ClinPred

0.015

GERP RS

0.72

Varity_R

0.050

gMVP

0.034

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