rs137852779

Positions:

• chr6-52438538-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018100.4(EFHC1):​c.520A>G​(p.Ile174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: EFHC1 NM_018100.4 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.18

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFHC1	NM_018100.4	c.520A>G	p.Ile174Val	missense_variant	3/11	ENST00000371068.11
EFHC1	NM_001172420.2	c.463A>G	p.Ile155Val	missense_variant	4/12
EFHC1	NR_033327.2	n.589A>G		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFHC1	ENST00000371068.11	c.520A>G	p.Ile174Val	missense_variant	3/11	1	NM_018100.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251104 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135726

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461782 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Absence seizure Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 12, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.0070	T;.;.;T;T;T;T;T;T;.;.;.;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D;D;.;D;D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.0058	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Benign	0.36	T
Polyphen		0.0010	.;.;.;B;.;.;.;.;.;.;.;.;.
Vest4		0.16, 0.16
MutPred		0.83		.;.;.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);.;.;.;
MVP		0.70
MPC		0.075
ClinPred		0.37	T
GERP RS		-1.8
Varity_R		0.029
gMVP		0.31

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: rs137852779; hg19: chr6-52303336;