rs7055196

Variant names:

• chrX-44245292-A-G
• rs7055196
• NM_025184.4:c.1111+2980T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EFHC2	NM_025184.4	c.1111+2980T>C		intron_variant	Intron 7 of 14	ENST00000420999.2	NP_079460.2
EFHC2	XM_047442535.1	c.1111+2980T>C		intron_variant	Intron 7 of 13		XP_047298491.1
EFHC2	XM_047442536.1	c.1111+2980T>C		intron_variant	Intron 7 of 14		XP_047298492.1
EFHC2	XM_006724562.3	c.523+2980T>C		intron_variant	Intron 6 of 13		XP_006724625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFHC2	ENST00000420999.2	c.1111+2980T>C		intron_variant	Intron 7 of 14	1	NM_025184.4	ENSP00000404232.2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 24434 AN: 111654 Hom.: 3346 Cov.: 23

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

African (AFR) AF: 0.497 AC: 15174 AN: 30548

American (AMR) AF: 0.295 AC: 3121 AN: 10565

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 319 AN: 2645

East Asian (EAS) AF: 0.0594 AC: 213 AN: 3583

South Asian (SAS) AF: 0.138 AC: 366 AN: 2652

European-Finnish (FIN) AF: 0.0377 AC: 231 AN: 6133

Middle Eastern (MID) AF: 0.0972 AC: 21 AN: 216

European-Non Finnish (NFE) AF: 0.0875 AC: 4649 AN: 53161

Other (OTH) AF: 0.209 AC: 319 AN: 1528

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
PhyloP100		-0.48
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: rs7055196; hg19: chrX-44104538;