7-100818628-A-G

Position:

chr7-100818628-A-G

Variant summary

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

The NM_004444.5(EPHB4):c.1314T>C(p.Ser438=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,610,268 control chromosomes in the GnomAD database, including 292,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24821 hom., cov: 32)

Exomes 𝑓: 0.60 ( 267416 hom. )

Consequence

EPHB4
NM_004444.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.14

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-100818628-A-G is Benign according to our data. Variant chr7-100818628-A-G is described in ClinVar as [Benign]. Clinvar id is 811643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-100818628-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 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.1314T>C	p.Ser438=	synonymous_variant	7/17	ENST00000358173.8
EPHB4	XM_017011816.2 linkuse as main transcript	c.1368T>C	p.Ser456=	synonymous_variant	7/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHB4	ENST00000358173.8 linkuse as main transcript	c.1314T>C	p.Ser438=	synonymous_variant	7/17	1	NM_004444.5	P1	P54760-1

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

85910

AN:

151828

Hom.:

24814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.611

AC:

150452

AN:

246310

Hom.:

46335

AF XY:

0.612

AC XY:

81630

AN XY:

133418

show subpopulations

Gnomad AFR exome

AF:

0.445

Gnomad AMR exome

AF:

0.696

Gnomad ASJ exome

AF:

0.539

Gnomad EAS exome

AF:

0.647

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.608

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.604

AC:

880797

AN:

1458322

Hom.:

267416

Cov.:

AF XY:

0.605

AC XY:

438860

AN XY:

725572

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.693

Gnomad4 ASJ exome

AF:

0.543

Gnomad4 EAS exome

AF:

0.664

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.603

Gnomad4 OTH exome

AF:

0.594

GnomAD4 genome

AF:

0.566

AC:

85949

AN:

151946

Hom.:

24821

Cov.:

AF XY:

0.570

AC XY:

42321

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.450

Gnomad4 AMR

AF:

0.661

Gnomad4 ASJ

AF:

0.559

Gnomad4 EAS

AF:

0.632

Gnomad4 SAS

AF:

0.608

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.604

Alfa

AF:

0.601

Hom.:

56184

Bravo

AF:

0.568

Asia WGS

AF:

0.577

AC:

2008

AN:

3478

EpiCase

AF:

0.615

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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	Sep 21, 2018	- -
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

- -

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. -

Capillary malformation-arteriovenous malformation 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.028

DANN

Benign

0.49

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