Genetic Variant EFCAB13:p.Thr33Ile (chr17-47335263-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_152347.5(EFCAB13):c.98C>T(p.Thr33Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,611,064 control chromosomes in the GnomAD database, including 144 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).

Frequency

Genomes: 𝑓 0.0088 ( 10 hom., cov: 32)

Exomes 𝑓: 0.012 ( 134 hom. )

Consequence

EFCAB13
NM_152347.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.168

Variant links:

Genes affected

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

EFCAB13 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042818785).

BP6

Variant 17-47335263-C-T is Benign according to our data. Variant chr17-47335263-C-T is described in ClinVar as [Benign]. Clinvar id is 3050458.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB13	NM_152347.5 link	c.98C>T	p.Thr33Ile	missense_variant	Exon 5 of 25	ENST00000331493.7	NP_689560.3	Q8IY85-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EFCAB13	ENST00000331493.7 link	c.98C>T	p.Thr33Ile	missense_variant	Exon 5 of 25	1	NM_152347.5	ENSP00000332111.2	Q8IY85-1
ENSG00000259753	ENST00000560629.1 link	n.*87C>T		non_coding_transcript_exon_variant	Exon 16 of 18	2		ENSP00000456711.2	H3BM21
ENSG00000259753	ENST00000560629.1 link	n.*87C>T		3_prime_UTR_variant	Exon 16 of 18	2		ENSP00000456711.2	H3BM21

Frequencies

GnomAD3 genomes

AF:

0.00880

AC:

1338

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00983

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00840

AC:

2089

AN:

248606

Hom.:

AF XY:

0.00865

AC XY:

1161

AN XY:

134288

show subpopulations

Gnomad AFR exome

AF:

0.00260

Gnomad AMR exome

AF:

0.00768

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00758

Gnomad FIN exome

AF:

0.00256

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.00907

GnomAD4 exome

AF:

0.0120

AC:

17525

AN:

1458864

Hom.:

134

Cov.:

AF XY:

0.0119

AC XY:

8607

AN XY:

725572

show subpopulations

Gnomad4 AFR exome

AF:

0.00231

Gnomad4 AMR exome

AF:

0.00849

Gnomad4 ASJ exome

AF:

0.00522

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00878

Gnomad4 FIN exome

AF:

0.00244

Gnomad4 NFE exome

AF:

0.0138

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00878

AC:

1336

AN:

152200

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

614

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00270

Gnomad4 AMR

AF:

0.00982

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00973

Gnomad4 FIN

AF:

0.00293

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00895

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.00857

AC:

1041

Asia WGS

AF:

0.00173

AC:

AN:

3474

EpiCase

AF:

0.0136

EpiControl

AF:

0.0157

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EFCAB13-related disorder

Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.78

DANN

Benign

0.65

DEOGEN2

Benign

0.0010

.;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.45

T;T;T;T

MetaRNN

Benign

0.0043

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;N;.;N

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-4.6

D;N;D;N

REVEL

Benign

0.14

Sift

Uncertain

0.027

D;D;T;T

Sift4G

Uncertain

0.049

D;T;T;T

Polyphen

0.063

.;B;.;.

Vest4

0.14, 0.083

MVP

0.030

MPC

0.16

ClinPred

0.011

GERP RS

-5.6

Varity_R

0.037

gMVP

0.013

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