Variant chr3-135259107-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000398015.8(EPHB1):c.2942C>T(p.Thr981Met) variant causes a missense change. The variant allele was found at a frequency of 0.00113 in 1,607,970 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. T981T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

EPHB1
ENST00000398015.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.08

Variant links:

Genes affected

EPHB1 (HGNC:3392): (EPH receptor B1) 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 is a receptor for ephrin-B family members. [provided by RefSeq, Jul 2008]

EPHB1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009133428).

BS2

High AC in GnomAd4 at 226 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB1	NM_004441.5 linkuse as main transcript	c.2942C>T	p.Thr981Met	missense_variant	16/16	ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8 linkuse as main transcript	c.2942C>T	p.Thr981Met	missense_variant	16/16	1	NM_004441.5	ENSP00000381097	P1	P54762-1
	ENST00000649588.1 linkuse as main transcript	n.229-872G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00149

AC:

226

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00118

AC:

284

AN:

239804

Hom.:

AF XY:

0.00121

AC XY:

157

AN XY:

129588

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad SAS exome

AF:

0.00267

Gnomad FIN exome

AF:

0.00199

Gnomad NFE exome

AF:

0.000846

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.00109

AC:

1587

AN:

1455774

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

812

AN XY:

723402

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.000278

Gnomad4 SAS exome

AF:

0.00251

Gnomad4 FIN exome

AF:

0.00231

Gnomad4 NFE exome

AF:

0.000962

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00148

AC:

226

AN:

152196

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000903

Hom.:

Bravo

AF:

0.00141

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00179

AC:

ESP6500EA

AF:

0.000962

AC:

ExAC

AF:

0.00123

AC:

149

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.0091

T;T

MetaSVM

Uncertain

0.061

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.37

MVP

0.70

MPC

1.2

ClinPred

0.026

GERP RS

5.6

Varity_R

0.076

gMVP

0.52

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over