7-100803561-G-A

Position:

chr7-100803561-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000358173.8(EPHB4):c.2864C>T(p.Ala955Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,605,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

EPHB4
ENST00000358173.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 10.0

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0103468).

BP6

Variant 7-100803561-G-A is Benign according to our data. Variant chr7-100803561-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2701266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000867 (132/152310) while in subpopulation AFR AF= 0.00298 (124/41572). AF 95% confidence interval is 0.00256. There are 0 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 132 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB4	NM_004444.5 linkuse as main transcript	c.2864C>T	p.Ala955Val	missense_variant	17/17	ENST00000358173.8	NP_004435.3
EPHB4	XM_017011816.2 linkuse as main transcript	c.2918C>T	p.Ala973Val	missense_variant	17/17		XP_016867305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHB4	ENST00000358173.8 linkuse as main transcript	c.2864C>T	p.Ala955Val	missense_variant	17/17	1	NM_004444.5	ENSP00000350896	P1	P54760-1
EPHB4	ENST00000360620.7 linkuse as main transcript	c.2708C>T	p.Ala903Val	missense_variant	16/16	1		ENSP00000353833
EPHB4	ENST00000487222.5 linkuse as main transcript	n.4065C>T		non_coding_transcript_exon_variant	16/16	1
EPHB4	ENST00000616502.4 linkuse as main transcript	c.*1329C>T		3_prime_UTR_variant	14/14	5		ENSP00000482702		P54760-3

Frequencies

GnomAD3 genomes

AF:

0.000867

AC:

132

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000276

AC:

AN:

239448

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

129268

show subpopulations

Gnomad AFR exome

AF:

0.00405

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000346

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000279

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000757

AC:

110

AN:

1452894

Hom.:

Cov.:

AF XY:

0.0000666

AC XY:

AN XY:

721250

show subpopulations

Gnomad4 AFR exome

AF:

0.00270

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000632

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000867

AC:

132

AN:

152310

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00298

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000153

Hom.:

Bravo

AF:

0.000846

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000329

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	EPHB4: BS1 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

D;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.5

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.68

T;T

Sift4G

Benign

1.0

T;T

Polyphen

1.0

D;D

Vest4

0.40

MVP

0.56

MPC

1.4

ClinPred

0.11

GERP RS

4.6

Varity_R

0.34

gMVP

0.35

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