rs3827791

Variant names:

• chr6-52468054-A-G
• rs3827791
• NM_018100.4:c.1138-1279A>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.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
• Publications: 3 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=-0.64).
• 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 rank	MANE	Protein	UniProt
EFHC1	NM_018100.4	c.1138-1279A>G		intron_variant	Intron 6 of 10	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.1081-1279A>G		intron_variant	Intron 7 of 11		NP_001165891.1
EFHC1	NR_033327.2	n.2464-1279A>G		intron_variant	Intron 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.1138-1279A>G		intron_variant	Intron 6 of 10	1	NM_018100.4	ENSP00000360107.4

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

African (AFR) AF: 0.0228 AC: 947 AN: 41560

American (AMR) AF: 0.108 AC: 1653 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 578 AN: 3472

East Asian (EAS) AF: 0.448 AC: 2319 AN: 5172

South Asian (SAS) AF: 0.202 AC: 974 AN: 4828

European-Finnish (FIN) AF: 0.0798 AC: 847 AN: 10608

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7458 AN: 67998

Other (OTH) AF: 0.0974 AC: 206 AN: 2116

Alfa AF: 0.111 Hom.: 562

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
PhyloP100		0.76
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: rs3827791; hg19: chr6-52332852;