Variant chr17-47345080-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152347.5(EFCAB13):c.499C>G(p.His167Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,602,540 control chromosomes in the GnomAD database, including 3 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

EFCAB13
NM_152347.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.73

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013456523).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB13	NM_152347.5 link	c.499C>G	p.His167Asp	missense_variant	8/25	ENST00000331493.7	NP_689560.3	Q8IY85-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EFCAB13	ENST00000331493.7 link	c.499C>G	p.His167Asp	missense_variant	8/25	1	NM_152347.5	ENSP00000332111.2	Q8IY85-1
EFCAB13	ENST00000517484.5 link	c.499C>G	p.His167Asp	missense_variant	8/22	2		ENSP00000430048.1	Q8IY85-2
EFCAB13	ENST00000517310.5 link	c.55C>G	p.His19Asp	missense_variant	9/11	2		ENSP00000466136.1	K7ELL9
EFCAB13	ENST00000520776.5 link	n.633C>G		non_coding_transcript_exon_variant	6/14	2

Frequencies

GnomAD3 genomes

AF:

0.000671

AC:

102

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000399

AC:

AN:

242866

Hom.:

AF XY:

0.000457

AC XY:

AN XY:

131314

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.0000312

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:

0.000827

Gnomad OTH exome

AF:

0.000339

GnomAD4 exome

AF:

0.00120

AC:

1745

AN:

1450322

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

830

AN XY:

721372

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.0000464

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00144

Gnomad4 OTH exome

AF:

0.00225

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152218

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00127

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000714

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000387

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

Apr 26, 2024

The c.499C>G (p.H167D) alteration is located in exon 8 (coding exon 5) of the EFCAB13 gene. This alteration results from a C to G substitution at nucleotide position 499, causing the histidine (H) at amino acid position 167 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.054

DANN

Benign

0.68

DEOGEN2

Benign

0.00039

.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.38

T;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.60

.;N;N

REVEL

Benign

0.034

Sift

Uncertain

0.025

.;D;T

Sift4G

Uncertain

0.041

D;T;T

Polyphen

0.0

.;B;.

Vest4

0.37, 0.37

MVP

0.014

MPC

0.19

ClinPred

0.0066

GERP RS

-7.0

Varity_R

0.041

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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