rs2230585

Positions:

chr7-100812975-G-A

Variant summary

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

The NM_004444.5(EPHB4):c.1890C>T(p.Cys630=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,613,700 control chromosomes in the GnomAD database, including 112,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8562 hom., cov: 33)

Exomes 𝑓: 0.37 ( 103551 hom. )

Consequence

EPHB4
NM_004444.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

EPHB4 (HGNC:3395): (EPH receptor B4) Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of 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. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development. [provided by RefSeq, Jul 2008]

EPHB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 7-100812975-G-A is Benign according to our data. Variant chr7-100812975-G-A is described in ClinVar as [Benign]. Clinvar id is 811000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-100812975-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHB4	NM_004444.5 linkuse as main transcript	c.1890C>T	p.Cys630=	synonymous_variant	12/17	ENST00000358173.8
EPHB4	XM_017011816.2 linkuse as main transcript	c.1944C>T	p.Cys648=	synonymous_variant	12/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHB4	ENST00000358173.8 linkuse as main transcript	c.1890C>T	p.Cys630=	synonymous_variant	12/17	1	NM_004444.5	P1	P54760-1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49027

AN:

151996

Hom.:

8558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.341

AC:

85538

AN:

250944

Hom.:

15284

AF XY:

0.343

AC XY:

46483

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.314

Gnomad SAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.423

Gnomad NFE exome

AF:

0.385

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.372

AC:

543540

AN:

1461584

Hom.:

103551

Cov.:

AF XY:

0.370

AC XY:

268864

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.275

Gnomad4 ASJ exome

AF:

0.439

Gnomad4 EAS exome

AF:

0.294

Gnomad4 SAS exome

AF:

0.258

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.390

Gnomad4 OTH exome

AF:

0.364

GnomAD4 genome

AF:

0.322

AC:

49043

AN:

152116

Hom.:

8562

Cov.:

AF XY:

0.320

AC XY:

23824

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.322

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.427

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.369

Hom.:

13348

Bravo

AF:

0.309

Asia WGS

AF:

0.283

AC:

985

AN:

3478

EpiCase

AF:

0.378

EpiControl

AF:

0.383

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 21, 2019	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Lymphatic malformation 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Capillary malformation-arteriovenous malformation 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2018

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.2

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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