rs7887763

Positions:

• chrX-44264531-C-T

Variant summary

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

The NM_025184.4(EFHC2):​c.383-3233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 111,130 control chromosomes in the GnomAD database, including 2,200 homozygotes. There are 5,787 hemizygotes in GnomAD. 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 0.19 (2200 hom., 5787 hem., cov: 22)
• Consequence: EFHC2 NM_025184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

EFHC2 (HGNC:26233): (EF-hand domain containing 2) This gene encodes a protein which contains three DM10 domains and three calcium-binding EF-hand motifs. A related protein is encoded by a gene on chromosome 6. It has been suggested that both proteins are involved in the development of epilepsy (PMID: 15258581, 16112844) and that this gene may be associated with fear recognition in individuals with Turner syndrome. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHC2	NM_025184.4	c.383-3233G>A		intron_variant		ENST00000420999.2	NP_079460.2
EFHC2	XM_006724562.3	c.-206-3233G>A		intron_variant			XP_006724625.1
EFHC2	XM_047442535.1	c.383-3233G>A		intron_variant			XP_047298491.1
EFHC2	XM_047442536.1	c.383-3233G>A		intron_variant			XP_047298492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC2	ENST00000420999.2	c.383-3233G>A		intron_variant		1	NM_025184.4	ENSP00000404232	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 20595 AN: 111076 Hom.: 2193 Cov.: 22 AF XY: 0.172 AC XY: 5740 AN XY: 33310

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0840

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.186 AC: 20648 AN: 111130 Hom.: 2200 Cov.: 22 AF XY: 0.173 AC XY: 5787 AN XY: 33374

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0581

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0384

Gnomad4 NFE AF: 0.0850

Gnomad4 OTH AF: 0.177

Alfa AF: 0.124 Hom.: 4654

Bravo AF: 0.220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.57

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: rs7887763; hg19: chrX-44123777;