rs3804505

Positions:

Variant summary

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

The ENST00000371068.11(EFHC1):c.545G>A(p.Arg182His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 1,613,812 control chromosomes in the GnomAD database, including 3,170 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R182C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.048 ( 240 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2930 hom. )

Consequence

EFHC1
ENST00000371068.11 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 1.34

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=0.0028097034).

BP6

Variant 6-52438563-G-A is Benign according to our data. Variant chr6-52438563-G-A is described in ClinVar as [Benign]. Clinvar id is 2063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52438563-G-A is described in Lovd as [Benign]. Variant chr6-52438563-G-A is described in Lovd as [Pathogenic].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFHC1	NM_018100.4 linkuse as main transcript	c.545G>A	p.Arg182His	missense_variant	3/11	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2 linkuse as main transcript	c.488G>A	p.Arg163His	missense_variant	4/12		NP_001165891.1
EFHC1	NR_033327.2 linkuse as main transcript	n.614G>A		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11 linkuse as main transcript	c.545G>A	p.Arg182His	missense_variant	3/11	1	NM_018100.4	ENSP00000360107	P1	Q5JVL4-1

Frequencies

GnomAD3 genomes

AF:

0.0475

AC:

7224

AN:

152040

Hom.:

235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0447

Gnomad ASJ

AF:

0.0450

Gnomad EAS

AF:

0.0726

Gnomad SAS

AF:

0.0722

Gnomad FIN

AF:

0.0897

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0597

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0603

AC:

15135

AN:

251004

Hom.:

552

AF XY:

0.0615

AC XY:

8348

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.0534

Gnomad ASJ exome

AF:

0.0481

Gnomad EAS exome

AF:

0.0821

Gnomad SAS exome

AF:

0.0687

Gnomad FIN exome

AF:

0.0870

Gnomad NFE exome

AF:

0.0599

Gnomad OTH exome

AF:

0.0579

GnomAD4 exome

AF:

0.0602

AC:

88055

AN:

1461652

Hom.:

2930

Cov.:

AF XY:

0.0602

AC XY:

43806

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00938

Gnomad4 AMR exome

AF:

0.0520

Gnomad4 ASJ exome

AF:

0.0501

Gnomad4 EAS exome

AF:

0.0603

Gnomad4 SAS exome

AF:

0.0687

Gnomad4 FIN exome

AF:

0.0893

Gnomad4 NFE exome

AF:

0.0604

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0476

AC:

7241

AN:

152160

Hom.:

240

Cov.:

AF XY:

0.0489

AC XY:

3636

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.0449

Gnomad4 ASJ

AF:

0.0450

Gnomad4 EAS

AF:

0.0723

Gnomad4 SAS

AF:

0.0729

Gnomad4 FIN

AF:

0.0897

Gnomad4 NFE

AF:

0.0597

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0534

Hom.:

636

Bravo

AF:

0.0423

TwinsUK

AF:

0.0677

AC:

251

ALSPAC

AF:

0.0568

AC:

219

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.0603

AC:

519

ExAC

AF:

0.0604

AC:

7329

Asia WGS

AF:

0.117

AC:

404

AN:

3478

EpiCase

AF:

0.0542

EpiControl

AF:

0.0543

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Myoclonic epilepsy, juvenile, susceptibility to, 1

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Aug 01, 2004

- -

Juvenile myoclonic epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 08, 2017

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0042

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

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.58

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

D;D;.;D;D;D;D;D;D;D;.;T;D

MetaRNN

Benign

0.0028

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

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

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.48

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

REVEL

Benign

0.030

Sift

Benign

0.20

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

Sift4G

Benign

0.26

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

Polyphen

0.0040

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

Vest4

0.047, 0.040

MPC

0.11

ClinPred

0.0026

GERP RS

0.80

Varity_R

0.032

gMVP

0.50

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