dbSNP rs9349626: EFHC1:c.573+10A>G (chr6-52438601-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_018100.4(EFHC1):c.573+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,142 control chromosomes in the GnomAD database, including 37,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3237 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34176 hom. )

Consequence

EFHC1
NM_018100.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.190

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 (BayesDel_noAF=-0.77).

BP6

Variant 6-52438601-A-G is Benign according to our data. Variant chr6-52438601-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 128969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52438601-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4 link	c.573+10A>G	intron_variant	Intron 3 of 10	ENST00000371068.11	NP_060570.2	Q5JVL4-1B2CKC5
EFHC1	NM_001172420.2 link	c.516+10A>G	intron_variant	Intron 4 of 11		NP_001165891.1	Q5JVL4-3B2CKC5
EFHC1	NR_033327.2 link	n.642+10A>G	intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11 link	c.573+10A>G		intron_variant	Intron 3 of 10	1	NM_018100.4	ENSP00000360107.4		Q5JVL4-1

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

28979

AN:

151994

Hom.:

3229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.237

AC:

59332

AN:

250182

Hom.:

8565

AF XY:

0.232

AC XY:

31473

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.218

Gnomad SAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.208

AC:

303681

AN:

1461028

Hom.:

34176

Cov.:

AF XY:

0.209

AC XY:

151789

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.453

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.253

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.191

AC:

29000

AN:

152114

Hom.:

3237

Cov.:

AF XY:

0.195

AC XY:

14535

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.196

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.187

Hom.:

898

Bravo

AF:

0.200

Asia WGS

AF:

0.215

AC:

745

AN:

3478

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 08, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.54

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