rs9357733

Variant names:

• chr6-52427338-A-G
• rs9357733
• NM_018100.4:c.285+3171A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018100.4(EFHC1):​c.285+3171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,996 control chromosomes in the GnomAD database, including 3,160 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3160 hom., cov: 32)
• Consequence: EFHC1 NM_018100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4	c.285+3171A>G		intron_variant	Intron 2 of 10	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.228+3171A>G		intron_variant	Intron 3 of 11		NP_001165891.1
EFHC1	NR_033327.2	n.354+3171A>G		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.285+3171A>G		intron_variant	Intron 2 of 10	1	NM_018100.4	ENSP00000360107.4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28803 AN: 151878 Hom.: 3152 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28823 AN: 151996 Hom.: 3160 Cov.: 32 AF XY: 0.194 AC XY: 14427 AN XY: 74308

African (AFR) AF: 0.130 AC: 5390 AN: 41472

American (AMR) AF: 0.334 AC: 5096 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1112 AN: 5172

South Asian (SAS) AF: 0.222 AC: 1068 AN: 4802

European-Finnish (FIN) AF: 0.190 AC: 2009 AN: 10558

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12931 AN: 67950

Other (OTH) AF: 0.177 AC: 373 AN: 2108

Alfa AF: 0.193 Hom.: 400

Bravo AF: 0.200

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9357733; hg19: chr6-52292136;