6-52469350-C-T

Position:

• chr6-52469350-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_018100.4(EFHC1):​c.1155C>T​(p.Asn385Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00039 in 1,613,952 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: EFHC1 NM_018100.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0900

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-52469350-C-T is Benign according to our data. Variant chr6-52469350-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 128960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.09 with no splicing effect.
• BS2: High AC in GnomAd4 at 298 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHC1	NM_018100.4	c.1155C>T	p.Asn385Asn	synonymous_variant	7/11	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.1098C>T	p.Asn366Asn	synonymous_variant	8/12		NP_001165891.1
EFHC1	NR_033327.2	n.2481C>T		non_coding_transcript_exon_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.1155C>T	p.Asn385Asn	synonymous_variant	7/11	1	NM_018100.4	ENSP00000360107.4

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 296 AN: 152154 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00668

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000557 AC: 140 AN: 251334 Hom.: 1 AF XY: 0.000412 AC XY: 56 AN XY: 135838

Gnomad AFR exome AF: 0.00726

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000226 AC: 331 AN: 1461680 Hom.: 1 Cov.: 30 AF XY: 0.000190 AC XY: 138 AN XY: 727136

Gnomad4 AFR exome AF: 0.00738

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.000679

GnomAD4 genome AF: 0.00196 AC: 298 AN: 152272 Hom.: 3 Cov.: 32 AF XY: 0.00200 AC XY: 149 AN XY: 74464

Gnomad4 AFR AF: 0.00671

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000717 Hom.: 0

Bravo AF: 0.00227

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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. -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 06, 2014	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 20, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 30, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.6
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs115913738; hg19: chr6-52334148;