rs137852781

Variant names:

• chr6-52454254-C-G
• rs137852781
• NM_018100.4:c.883C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-52454254-C-G
• chr6-52454254-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018100.4(EFHC1):​c.883C>G​(p.Gln295Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EFHC1 NM_018100.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018100.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC1	NM_018100.4	MANE Select	c.883C>G	p.Gln295Glu	missense	Exon 5 of 11	NP_060570.2
	EFHC1	NM_001172420.2		c.826C>G	p.Gln276Glu	missense	Exon 6 of 12	NP_001165891.1
	EFHC1	NR_033327.2		n.2209C>G		non_coding_transcript_exon	Exon 4 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC1	ENST00000371068.11	TSL:1 MANE Select	c.883C>G	p.Gln295Glu	missense	Exon 5 of 11	ENSP00000360107.4
	EFHC1	ENST00000637340.1	TSL:1	n.2808C>G		non_coding_transcript_exon	Exon 4 of 10
	EFHC1	ENST00000637353.1	TSL:5	c.883C>G	p.Gln295Glu	missense	Exon 5 of 11	ENSP00000490441.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Benign	0.31	T
Polyphen		0.37	B
Vest4		0.66
MutPred		0.54		Gain of ubiquitination at K299 (P = 0.0599)
MVP		0.74
MPC		0.20
ClinPred		0.63	D
GERP RS		5.9
Varity_R		0.24
gMVP		0.61
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs137852781; hg19: chr6-52319052;