rs3827791

chr6-52468054-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018100.4(EFHC1):c.1138-1279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 152,244 control chromosomes in the GnomAD database, including 1,292 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 0.099 (1292 hom., cov: 32)
• Consequence: EFHC1 NM_018100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFHC1	NM_018100.4	c.1138-1279A>G		intron_variant		ENST00000371068.11
EFHC1	NM_001172420.2	c.1081-1279A>G		intron_variant
EFHC1	NR_033327.2	n.2464-1279A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFHC1	ENST00000371068.11	c.1138-1279A>G		intron_variant		1	NM_018100.4	P1

Frequencies

GnomAD3 genomes AF: 0.0993 AC: 15106 AN: 152126 Hom.: 1292 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0798

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0979

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

GnomAD4 genome AF: 0.0992 AC: 15102 AN: 152244 Hom.: 1292 Cov.: 32 AF XY: 0.101 AC XY: 7521 AN XY: 74444

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.0798

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.111 Hom.: 515

Bravo AF: 0.0969

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	14
Dann	Benign	0.82

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: rs3827791; hg19: chr6-52332852;