Variant rs1054750 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_005233.6(EPHA3):c.2802T>C(p.Gly934Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,613,026 control chromosomes in the GnomAD database, including 45,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.19 ( 3374 hom., cov: 32)

Exomes 𝑓: 0.23 ( 42115 hom. )

Consequence

EPHA3
NM_005233.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.25

Variant links:

Genes affected

EPHA3 (HGNC:3387): (EPH receptor A3) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

EPHA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 3-89472575-T-C is Benign according to our data. Variant chr3-89472575-T-C is described in ClinVar as [Benign]. Clinvar id is 3055487.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA3	NM_005233.6 linkuse as main transcript	c.2802T>C	p.Gly934Gly	synonymous_variant	16/17	ENST00000336596.7	NP_005224.2	P29320-1A0A140VJJ0Q6P4R6
EPHA3	XM_005264715.4 linkuse as main transcript	c.2799T>C	p.Gly933Gly	synonymous_variant	16/17		XP_005264772.1
EPHA3	NM_001410778.1 linkuse as main transcript	c.2749+53T>C		intron_variant			NP_001397707.1
EPHA3	XM_047447673.1 linkuse as main transcript	c.2746+53T>C		intron_variant			XP_047303629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA3	ENST00000336596.7 linkuse as main transcript	c.2802T>C	p.Gly934Gly	synonymous_variant	16/17	1	NM_005233.6	ENSP00000337451.2		P29320-1
EPHA3	ENST00000494014.1 linkuse as main transcript	c.2749+53T>C		intron_variant		1		ENSP00000419190.1		C9JXA2

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29051

AN:

151974

Hom.:

3373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0787

Gnomad SAS

AF:

0.0840

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.204

AC:

51156

AN:

250650

Hom.:

6219

AF XY:

0.201

AC XY:

27287

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.0879

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.143

Gnomad EAS exome

AF:

0.0825

Gnomad SAS exome

AF:

0.0888

Gnomad FIN exome

AF:

0.366

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.231

AC:

337281

AN:

1460934

Hom.:

42115

Cov.:

AF XY:

0.227

AC XY:

164825

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.0827

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.0597

Gnomad4 SAS exome

AF:

0.0912

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.191

AC:

29061

AN:

152092

Hom.:

3374

Cov.:

AF XY:

0.192

AC XY:

14304

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0916

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.0791

Gnomad4 SAS

AF:

0.0839

Gnomad4 FIN

AF:

0.368

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.226

Hom.:

5292

Bravo

AF:

0.176

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EPHA3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.1

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over