rs505760

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018100.4(EFHC1):c.1069G>A(p.Glu357Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000287 in 1,614,082 control chromosomes in the GnomAD database, including 2 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 (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

EFHC1
NM_018100.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.10

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066770017).

BP6

Variant 6-52465047-G-A is Benign according to our data. Variant chr6-52465047-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52465047-G-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 243 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4 link	c.1069G>A	p.Glu357Lys	missense_variant	Exon 6 of 11	ENST00000371068.11	NP_060570.2	Q5JVL4-1B2CKC5
EFHC1	NM_001172420.2 link	c.1012G>A	p.Glu338Lys	missense_variant	Exon 7 of 12		NP_001165891.1	Q5JVL4-3B2CKC5
EFHC1	NR_033327.2 link	n.2395G>A		non_coding_transcript_exon_variant	Exon 5 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11 link	c.1069G>A	p.Glu357Lys	missense_variant	Exon 6 of 11	1	NM_018100.4	ENSP00000360107.4		Q5JVL4-1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

244

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000481

AC:

121

AN:

251370

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00732

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000150

AC:

220

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00579

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00160

AC:

243

AN:

152270

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00573

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000342

Hom.:

Bravo

AF:

0.00175

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000544

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 27, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely 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

- -

not specified

Benign:1

Aug 19, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Benign:1

Dec 09, 2024

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

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

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

Eigen

Benign

-0.13

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.96

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

MetaRNN

Benign

0.0067

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

.;.;.;L;.;.;.;.;.;.;.;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.84

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

REVEL

Benign

0.083

Sift

Benign

0.33

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

Sift4G

Benign

0.77

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

Polyphen

0.015

.;.;.;B;.;.;.;.;.;.;.;.;.

Vest4

0.23, 0.22

MVP

0.77

MPC

0.097

ClinPred

0.027

GERP RS

5.4

Varity_R

0.26

gMVP

0.31

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