rs719395

Variant names:

• chr6-52426129-T-C
• rs719395
• NM_018100.4:c.285+1962T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-52426129-T-C
• chr6-52426129-T-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+1962T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,084 control chromosomes in the GnomAD database, including 11,479 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 0.37 (11479 hom., cov: 32)
• Consequence: EFHC1 NM_018100.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFHC1	NM_018100.4	c.285+1962T>C		intron_variant	Intron 2 of 10	ENST00000371068.11	NP_060570.2
EFHC1	NM_001172420.2	c.228+1962T>C		intron_variant	Intron 3 of 11		NP_001165891.1
EFHC1	NR_033327.2	n.354+1962T>C		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC1	ENST00000371068.11	c.285+1962T>C		intron_variant	Intron 2 of 10	1	NM_018100.4	ENSP00000360107.4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56493 AN: 151966 Hom.: 11465 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.372 AC: 56530 AN: 152084 Hom.: 11479 Cov.: 32 AF XY: 0.369 AC XY: 27390 AN XY: 74312

African (AFR) AF: 0.241 AC: 9981 AN: 41500

American (AMR) AF: 0.307 AC: 4694 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1327 AN: 3472

East Asian (EAS) AF: 0.135 AC: 702 AN: 5186

South Asian (SAS) AF: 0.350 AC: 1692 AN: 4832

European-Finnish (FIN) AF: 0.532 AC: 5606 AN: 10538

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31230 AN: 67960

Other (OTH) AF: 0.376 AC: 792 AN: 2106

Alfa AF: 0.421 Hom.: 52956

Bravo AF: 0.347

Asia WGS AF: 0.304 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.68
PhyloP100		-1.6
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: rs719395; hg19: chr6-52290927;