chr6-52479101-T-C

Variant names:

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.1343T>C(p.Met448Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,614,020 control chromosomes in the GnomAD database, including 2,319 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 883 hom., cov: 32)

Exomes 𝑓: 0.034 ( 1436 hom. )

Consequence

EFHC1
NM_018100.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.69

Publications

21 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=0.001758635).

BP6

Variant 6-52479101-T-C is Benign according to our data. Variant chr6-52479101-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4 link	c.1343T>C	p.Met448Thr	missense_variant	Exon 8 of 11	ENST00000371068.11	NP_060570.2	Q5JVL4-1B2CKC5
EFHC1	NM_001172420.2 link	c.1286T>C	p.Met429Thr	missense_variant	Exon 9 of 12		NP_001165891.1	Q5JVL4-3B2CKC5
EFHC1	NR_033327.2 link	n.2669T>C		non_coding_transcript_exon_variant	Exon 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11 link	c.1343T>C	p.Met448Thr	missense_variant	Exon 8 of 11	1	NM_018100.4	ENSP00000360107.4		Q5JVL4-1

Frequencies

GnomAD3 genomes

AF:

0.0747

AC:

11366

AN:

152086

Hom.:

881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0427

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0607

GnomAD2 exomes

AF:

0.0355

AC:

8920

AN:

251346

AF XY:

0.0316

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0254

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0212

Gnomad NFE exome

AF:

0.0327

Gnomad OTH exome

AF:

0.0290

GnomAD4 exome

AF:

0.0339

AC:

49496

AN:

1461816

Hom.:

1436

Cov.:

AF XY:

0.0326

AC XY:

23715

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.201

AC:

6725

AN:

33470

American (AMR)

AF:

0.0274

AC:

1226

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0125

AC:

326

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0111

AC:

954

AN:

86256

European-Finnish (FIN)

AF:

0.0224

AC:

1196

AN:

53418

Middle Eastern (MID)

AF:

0.0507

AC:

292

AN:

5758

European-Non Finnish (NFE)

AF:

0.0327

AC:

36332

AN:

1111968

Other (OTH)

AF:

0.0405

AC:

2443

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

2805

5609

8414

11218

14023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1404

2808

4212

5616

7020

<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:

0.0748

AC:

11384

AN:

152204

Hom.:

883

Cov.:

AF XY:

0.0728

AC XY:

5420

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.193

AC:

8022

AN:

41504

American (AMR)

AF:

0.0426

AC:

652

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0118

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0222

AC:

235

AN:

10608

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0325

AC:

2209

AN:

68004

Other (OTH)

AF:

0.0605

AC:

128

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

494

989

1483

1978

2472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0448

Hom.:

1307

Bravo

AF:

0.0820

TwinsUK

AF:

0.0380

AC:

141

ALSPAC

AF:

0.0298

AC:

115

ESP6500AA

AF:

0.196

AC:

864

ESP6500EA

AF:

0.0298

AC:

256

ExAC

AF:

0.0389

AC:

4728

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0364

EpiControl

AF:

0.0359

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 08, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 30, 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

0.12

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.059

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

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

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

MetaRNN

Benign

0.0018

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

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.63

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

PhyloP100

2.7

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.9

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

REVEL

Benign

0.050

Sift

Benign

0.63

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

Sift4G

Benign

1.0

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

Polyphen

0.0010

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

Vest4

0.20, 0.13

MPC

0.11

ClinPred

0.0097

GERP RS

3.6

Varity_R

0.17

gMVP

0.52

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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