rs3804505

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018100.4(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. 16/21 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. R182C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.048 ( 240 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2930 hom. )

Consequence

EFHC1
NM_018100.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.34

Publications

30 publications found

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 Gene-Disease associations (from GenCC):

juvenile myoclonic epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

EFHC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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/Likely_benign. ClinVar VariationId is 2063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
EFHC1	NM_018100.4 link	c.545G>A	p.Arg182His	missense_variant	Exon 3 of 11	ENST00000371068.11	NP_060570.2	Q5JVL4-1B2CKC5
EFHC1	NM_001172420.2 link	c.488G>A	p.Arg163His	missense_variant	Exon 4 of 12		NP_001165891.1	Q5JVL4-3B2CKC5
EFHC1	NR_033327.2 link	n.614G>A		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.545G>A	p.Arg182His	missense_variant	Exon 3 of 11	1	NM_018100.4	ENSP00000360107.4		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

GnomAD2 exomes

AF:

0.0603

AC:

15135

AN:

251004

AF XY:

0.0615

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 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

African (AFR)

AF:

0.00938

AC:

314

AN:

33468

American (AMR)

AF:

0.0520

AC:

2323

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

1310

AN:

26130

East Asian (EAS)

AF:

0.0603

AC:

2394

AN:

39696

South Asian (SAS)

AF:

0.0687

AC:

5926

AN:

86254

European-Finnish (FIN)

AF:

0.0893

AC:

4768

AN:

53410

Middle Eastern (MID)

AF:

0.0309

AC:

178

AN:

5766

European-Non Finnish (NFE)

AF:

0.0604

AC:

67147

AN:

1111834

Other (OTH)

AF:

0.0612

AC:

3695

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

4478

8956

13433

17911

22389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2536

5072

7608

10144

12680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0476

AC:

7241

AN:

152160

Hom.:

240

Cov.:

AF XY:

0.0489

AC XY:

3636

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0117

AC:

487

AN:

41530

American (AMR)

AF:

0.0449

AC:

685

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0450

AC:

156

AN:

3468

East Asian (EAS)

AF:

0.0723

AC:

375

AN:

5184

South Asian (SAS)

AF:

0.0729

AC:

351

AN:

4816

European-Finnish (FIN)

AF:

0.0897

AC:

950

AN:

10586

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0597

AC:

4056

AN:

67996

Other (OTH)

AF:

0.0464

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

352

704

1055

1407

1759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0533

Hom.:

1156

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

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

- -

Myoclonic epilepsy, juvenile, susceptibility to, 1

Uncertain:1

Aug 01, 2004

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Juvenile myoclonic epilepsy

Benign:1

May 08, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

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

0.062

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

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;.;.;.;.;.;.;.;.;.

PhyloP100

1.3

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

PromoterAI

0.0068

Neutral

(source)

Varity_R

0.032

gMVP

0.50

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over