Variant 2-221443506-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000281821.7(EPHA4):c.1875A>G(p.Lys625=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,613,282 control chromosomes in the GnomAD database, including 1,630 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 463 hom., cov: 32)

Exomes 𝑓: 0.019 ( 1167 hom. )

Consequence

EPHA4
ENST00000281821.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.20

Variant links:

Genes affected

EPHA4 (HGNC:3388): (EPH receptor A4) 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

EPHA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 2-221443506-T-C is Benign according to our data. Variant chr2-221443506-T-C is described in ClinVar as [Benign]. Clinvar id is 1170394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EPHA4	NM_004438.5 linkuse as main transcript	c.1875A>G	p.Lys625=	synonymous_variant	10/18	ENST00000281821.7	NP_004429.1
EPHA4	NM_001304536.2 linkuse as main transcript	c.1875A>G	p.Lys625=	synonymous_variant	11/19		NP_001291465.1
EPHA4	NM_001363748.2 linkuse as main transcript	c.1875A>G	p.Lys625=	synonymous_variant	10/18		NP_001350677.1
EPHA4	NM_001304537.2 linkuse as main transcript	c.1722A>G	p.Lys574=	synonymous_variant	9/17		NP_001291466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA4	ENST00000281821.7 linkuse as main transcript	c.1875A>G	p.Lys625=	synonymous_variant	10/18	1	NM_004438.5	ENSP00000281821	P1	P54764-1
EPHA4	ENST00000409854.5 linkuse as main transcript	c.1875A>G	p.Lys625=	synonymous_variant	10/17	1		ENSP00000386276
EPHA4	ENST00000409938.5 linkuse as main transcript	c.1875A>G	p.Lys625=	synonymous_variant	11/18	2		ENSP00000386829	P1	P54764-1

Frequencies

GnomAD3 genomes

AF:

0.0551

AC:

8375

AN:

151934

Hom.:

461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0764

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.0933

Gnomad SAS

AF:

0.0760

Gnomad FIN

AF:

0.00603

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.00584

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0453

AC:

11392

AN:

251300

Hom.:

596

AF XY:

0.0420

AC XY:

5701

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.0935

Gnomad SAS exome

AF:

0.0766

Gnomad FIN exome

AF:

0.00541

Gnomad NFE exome

AF:

0.00589

Gnomad OTH exome

AF:

0.0330

GnomAD4 exome

AF:

0.0193

AC:

28188

AN:

1461230

Hom.:

1167

Cov.:

AF XY:

0.0203

AC XY:

14748

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.0737

Gnomad4 FIN exome

AF:

0.00515

Gnomad4 NFE exome

AF:

0.00509

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.0553

AC:

8401

AN:

152052

Hom.:

463

Cov.:

AF XY:

0.0561

AC XY:

4169

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.0765

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.0937

Gnomad4 SAS

AF:

0.0753

Gnomad4 FIN

AF:

0.00603

Gnomad4 NFE

AF:

0.00584

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0151

Hom.:

142

Bravo

AF:

0.0658

Asia WGS

AF:

0.0910

AC:

316

AN:

3476

EpiCase

AF:

0.00796

EpiControl

AF:

0.00723

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

9.4

DANN

Benign

0.63

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