rs9349626

chr6-52438601-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.190

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
EFHC1	NM_018100.4	c.573+10A>G		intron_variant		ENST00000371068.11
EFHC1	NM_001172420.2	c.516+10A>G		intron_variant
EFHC1	NR_033327.2	n.642+10A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFHC1	ENST00000371068.11	c.573+10A>G		intron_variant		1	NM_018100.4	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28979 AN: 151994 Hom.: 3229 Cov.: 32

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

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.: 35 AF XY: 0.209 AC XY: 151789 AN XY: 726852

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.: 32 AF XY: 0.195 AC XY: 14535 AN XY: 74366

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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. -

Juvenile myoclonic epilepsy Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
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

Invitae

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
BayesDel_noAF	Benign	-0.77
Cadd	Benign	13
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

Other links and lift over

dbSNP: rs9349626; hg19: chr6-52303399; COSMIC: COSV64135347; COSMIC: COSV64135347;