chr6-52438493-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018100.4(EFHC1):c.475C>T(p.Arg159Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,778 control chromosomes in the GnomAD database, including 11,090 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R159G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.098 ( 821 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10269 hom. )

Consequence

EFHC1
NM_018100.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

EFHC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014902949).

BP6

Variant 6-52438493-C-T is Benign according to our data. Variant chr6-52438493-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 128968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52438493-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4 link	c.475C>T	p.Arg159Trp	missense_variant	Exon 3 of 11	ENST00000371068.11	NP_060570.2	Q5JVL4-1B2CKC5
EFHC1	NM_001172420.2 link	c.418C>T	p.Arg140Trp	missense_variant	Exon 4 of 12		NP_001165891.1	Q5JVL4-3B2CKC5
EFHC1	NR_033327.2 link	n.544C>T		non_coding_transcript_exon_variant	Exon 3 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11 link	c.475C>T	p.Arg159Trp	missense_variant	Exon 3 of 11	1	NM_018100.4	ENSP00000360107.4		Q5JVL4-1

Frequencies

GnomAD3 genomes

AF:

0.0979

AC:

14878

AN:

152016

Hom.:

823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0554

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.0375

Gnomad SAS

AF:

0.0776

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.102

AC:

25501

AN:

251084

Hom.:

1491

AF XY:

0.104

AC XY:

14064

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0515

Gnomad AMR exome

AF:

0.0772

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0362

Gnomad SAS exome

AF:

0.0831

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.127

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.114

AC:

166554

AN:

1461644

Hom.:

10269

Cov.:

AF XY:

0.114

AC XY:

82864

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0547

Gnomad4 AMR exome

AF:

0.0798

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.0430

Gnomad4 SAS exome

AF:

0.0827

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.0978

AC:

14882

AN:

152134

Hom.:

821

Cov.:

AF XY:

0.0984

AC XY:

7321

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0553

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.0374

Gnomad4 SAS

AF:

0.0777

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.120

Hom.:

1761

Bravo

AF:

0.0980

TwinsUK

AF:

0.118

AC:

438

ALSPAC

AF:

0.125

AC:

482

ESP6500AA

AF:

0.0563

AC:

248

ESP6500EA

AF:

0.123

AC:

1057

ExAC

AF:

0.100

AC:

12170

EpiCase

AF:

0.135

EpiControl

AF:

0.138

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Juvenile myoclonic epilepsy

Benign:2

May 04, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.;.;T;T;T;T;T;T;.;.;.;.

Eigen

Benign

-0.036

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.12

LIST_S2

Pathogenic

0.98

D;D;.;D;D;D;D;D;D;D;.;D;D

MetaRNN

Benign

0.0015

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.4

.;.;.;M;.;.;.;.;.;.;.;.;.

PrimateAI

Benign

0.19

PROVEAN

Benign

-2.3

.;.;.;N;.;.;.;.;.;.;.;.;N

REVEL

Benign

0.18

Sift

Benign

0.18

.;.;.;T;.;.;.;.;.;.;.;.;T

Sift4G

Benign

0.18

.;.;.;T;.;.;.;.;.;.;.;.;T

Polyphen

0.96

.;.;.;D;.;.;.;.;.;.;.;.;.

Vest4

0.18, 0.099

MPC

0.19

ClinPred

0.019

GERP RS

2.7

Varity_R

0.055

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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