rs7055196

Positions:

• chrX-44245292-A-G

Variant summary

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

The NM_025184.4(EFHC2):​c.1111+2980T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 111,710 control chromosomes in the GnomAD database, including 3,354 homozygotes. There are 6,944 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 0.22 (3354 hom., 6944 hem., cov: 23)
• Consequence: EFHC2 NM_025184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHC2	NM_025184.4	c.1111+2980T>C		intron_variant		ENST00000420999.2	NP_079460.2
EFHC2	XM_047442535.1	c.1111+2980T>C		intron_variant			XP_047298491.1
EFHC2	XM_047442536.1	c.1111+2980T>C		intron_variant			XP_047298492.1
EFHC2	XM_006724562.3	c.523+2980T>C		intron_variant			XP_006724625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC2	ENST00000420999.2	c.1111+2980T>C		intron_variant		1	NM_025184.4	ENSP00000404232.2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 24434 AN: 111654 Hom.: 3346 Cov.: 23 AF XY: 0.203 AC XY: 6892 AN XY: 33872

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0598

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0844

Gnomad NFE AF: 0.0875

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.219 AC: 24498 AN: 111710 Hom.: 3354 Cov.: 23 AF XY: 0.205 AC XY: 6944 AN XY: 33938

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0875

Gnomad4 OTH AF: 0.209

Alfa AF: 0.160 Hom.: 995

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.59
DANN	Benign	0.72

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: rs7055196; hg19: chrX-44104538;