Variant 3-135166038-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_004441.5(EPHB1):c.1656C>T(p.Phe552=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,613,826 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 18 hom. )

Consequence

EPHB1
NM_004441.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.189

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 3-135166038-C-T is Benign according to our data. Variant chr3-135166038-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 717504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.189 with no splicing effect.

BS2

High AC in GnomAd4 at 448 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHB1	NM_004441.5 linkuse as main transcript	c.1656C>T	p.Phe552=	synonymous_variant	8/16	ENST00000398015.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHB1	ENST00000398015.8 linkuse as main transcript	c.1656C>T	p.Phe552=	synonymous_variant	8/16	1	NM_004441.5	P1	P54762-1
	ENST00000649588.1 linkuse as main transcript	n.329-7710G>A		intron_variant, non_coding_transcript_variant
EPHB1	ENST00000647596.1 linkuse as main transcript	c.1656C>T	p.Phe552=	synonymous_variant	8/16
EPHB1	ENST00000493838.1 linkuse as main transcript	c.339C>T	p.Phe113=	synonymous_variant	6/14	2			P54762-5

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

448

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00315

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00462

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00308

AC:

768

AN:

249282

Hom.:

AF XY:

0.00325

AC XY:

439

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.000969

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00483

Gnomad OTH exome

AF:

0.00611

GnomAD4 exome

AF:

0.00325

AC:

4748

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2430

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00264

Gnomad4 FIN exome

AF:

0.000581

Gnomad4 NFE exome

AF:

0.00358

Gnomad4 OTH exome

AF:

0.00333

GnomAD4 genome

AF:

0.00294

AC:

448

AN:

152178

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000940

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00462

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00306

Asia WGS

AF:

0.00202

AC:

AN:

3478

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	Mar 01, 2023	EPHB1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jun 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

2.6

DANN

Benign

0.75

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