7-100813656-T-C

Position:

chr7-100813656-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004444.5(EPHB4):c.1752A>G(p.Gly584Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,613,392 control chromosomes in the GnomAD database, including 293,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 25521 hom., cov: 31)

Exomes 𝑓: 0.60 ( 268233 hom. )

Consequence

EPHB4
NM_004444.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0220

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:

EPHB4 (HGNC:):

EPHB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-100813656-T-C is Benign according to our data. Variant chr7-100813656-T-C is described in ClinVar as [Benign]. Clinvar id is 811646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-100813656-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.022 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB4	NM_004444.5 linkuse as main transcript	c.1752A>G	p.Gly584Gly	synonymous_variant	10/17	ENST00000358173.8	NP_004435.3
EPHB4	XM_017011816.2 linkuse as main transcript	c.1806A>G	p.Gly602Gly	synonymous_variant	10/17		XP_016867305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHB4	ENST00000358173.8 linkuse as main transcript	c.1752A>G	p.Gly584Gly	synonymous_variant	10/17	1	NM_004444.5	ENSP00000350896.3		P54760-1

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87384

AN:

151738

Hom.:

25515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.666

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.613

GnomAD3 exomes

AF:

0.614

AC:

154237

AN:

251370

Hom.:

47741

AF XY:

0.614

AC XY:

83404

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.480

Gnomad AMR exome

AF:

0.700

Gnomad ASJ exome

AF:

0.540

Gnomad EAS exome

AF:

0.646

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.577

Gnomad NFE exome

AF:

0.609

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.604

AC:

883387

AN:

1461538

Hom.:

268233

Cov.:

AF XY:

0.605

AC XY:

440033

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.488

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.543

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.603

Gnomad4 OTH exome

AF:

0.597

GnomAD4 genome

AF:

0.576

AC:

87420

AN:

151854

Hom.:

25521

Cov.:

AF XY:

0.580

AC XY:

43016

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.484

Gnomad4 AMR

AF:

0.666

Gnomad4 ASJ

AF:

0.560

Gnomad4 EAS

AF:

0.626

Gnomad4 SAS

AF:

0.608

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.604

Gnomad4 OTH

AF:

0.613

Alfa

AF:

0.597

Hom.:

33021

Bravo

AF:

0.579

Asia WGS

AF:

0.576

AC:

2005

AN:

3478

EpiCase

AF:

0.616

EpiControl

AF:

0.610

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	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.56

CADD

Benign

7.8

DANN

Benign

0.57

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