Variant rs2278107 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004440.4(EPHA7):c.412A>G(p.Ile138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,613,988 control chromosomes in the GnomAD database, including 1,801 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.035 ( 170 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1631 hom. )

Consequence

EPHA7
NM_004440.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.07

Variant links:

Genes affected

EPHA7 (HGNC:3390): (EPH receptor A7) 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. Increased expression of this gene is associated with multiple forms of carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

EPHA7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017443001).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA7	NM_004440.4 link	c.412A>G	p.Ile138Val	missense_variant	3/17	ENST00000369303.9	NP_004431.1	Q15375-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA7	ENST00000369303.9 link	c.412A>G	p.Ile138Val	missense_variant	3/17	1	NM_004440.4	ENSP00000358309.4		Q15375-1

Frequencies

GnomAD3 genomes

AF:

0.0354

AC:

5385

AN:

152174

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00753

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0704

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.0606

Gnomad FIN

AF:

0.0364

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0335

Gnomad OTH

AF:

0.0474

GnomAD3 exomes

AF:

0.0527

AC:

13231

AN:

251136

Hom.:

616

AF XY:

0.0508

AC XY:

6895

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00714

Gnomad AMR exome

AF:

0.0946

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.0570

Gnomad FIN exome

AF:

0.0347

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0473

GnomAD4 exome

AF:

0.0392

AC:

57329

AN:

1461696

Hom.:

1631

Cov.:

AF XY:

0.0396

AC XY:

28809

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00580

Gnomad4 AMR exome

AF:

0.0913

Gnomad4 ASJ exome

AF:

0.0155

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.0581

Gnomad4 FIN exome

AF:

0.0363

Gnomad4 NFE exome

AF:

0.0331

Gnomad4 OTH exome

AF:

0.0440

GnomAD4 genome

AF:

0.0354

AC:

5387

AN:

152292

Hom.:

170

Cov.:

AF XY:

0.0370

AC XY:

2759

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00751

Gnomad4 AMR

AF:

0.0704

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.166

Gnomad4 SAS

AF:

0.0611

Gnomad4 FIN

AF:

0.0364

Gnomad4 NFE

AF:

0.0335

Gnomad4 OTH

AF:

0.0502

Alfa

AF:

0.0371

Hom.:

417

Bravo

AF:

0.0363

TwinsUK

AF:

0.0321

AC:

119

ALSPAC

AF:

0.0317

AC:

122

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.0299

AC:

257

ExAC

AF:

0.0498

AC:

6040

Asia WGS

AF:

0.0960

AC:

331

AN:

3478

EpiCase

AF:

0.0331

EpiControl

AF:

0.0315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.019

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.086

Sift

Benign

0.12

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.010

B;B

Vest4

0.10

MPC

0.32

ClinPred

0.018

GERP RS

4.3

Varity_R

0.18

gMVP

0.36

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over