Genetic Variant NM_017449.5:c.1428+302C>T (chr1-22882785-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017449.5(EPHB2):c.1428+302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 371,658 control chromosomes in the GnomAD database, including 36,093 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 13079 hom., cov: 33)

Exomes 𝑓: 0.44 ( 23014 hom. )

Consequence

EPHB2
NM_017449.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.342

Variant links:

Genes affected

EPHB2 (HGNC:3393): (EPH receptor B2) This gene encodes a member of the Eph receptor family of receptor tyrosine kinase transmembrane glycoproteins. These receptors are composed of an N-terminal glycosylated ligand-binding domain, a transmembrane region and an intracellular kinase domain. They bind ligands called ephrins and are involved in diverse cellular processes including motility, division, and differentiation. A distinguishing characteristic of Eph-ephrin signaling is that both receptors and ligands are competent to transduce a signaling cascade, resulting in bidirectional signaling. This protein belongs to a subgroup of the Eph receptors called EphB. Proteins of this subgroup are distinguished from other members of the family by sequence homology and preferential binding affinity for membrane-bound ephrin-B ligands. Allelic variants are associated with prostate and brain cancer susceptibility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

EPHB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB2	NM_017449.5 link	c.1428+302C>T		intron_variant	Intron 6 of 15	ENST00000374630.8	NP_059145.2	P29323-2Q6NVW1Q4LE53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB2	ENST00000374630.8 link	c.1428+302C>T		intron_variant	Intron 6 of 15	1	NM_017449.5	ENSP00000363761.3		P29323-2
EPHB2	ENST00000374627.1 link	c.1410+302C>T		intron_variant	Intron 6 of 14	5		ENSP00000363758.1		B1AKC9

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56605

AN:

152062

Hom.:

13075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0956

Gnomad AMI

AF:

0.450

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.401

GnomAD4 exome

AF:

0.441

AC:

96782

AN:

219478

Hom.:

23014

Cov.:

AF XY:

0.421

AC XY:

49756

AN XY:

118066

show subpopulations

Gnomad4 AFR exome

AF:

0.0917

Gnomad4 AMR exome

AF:

0.534

Gnomad4 ASJ exome

AF:

0.472

Gnomad4 EAS exome

AF:

0.323

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.502

Gnomad4 NFE exome

AF:

0.509

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.372

AC:

56613

AN:

152180

Hom.:

13079

Cov.:

AF XY:

0.370

AC XY:

27512

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0953

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.463

Gnomad4 EAS

AF:

0.313

Gnomad4 SAS

AF:

0.259

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.505

Gnomad4 OTH

AF:

0.400

Alfa

AF:

0.449

Hom.:

2695

Bravo

AF:

0.365

Asia WGS

AF:

0.280

AC:

975

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.6

DANN

Benign

0.82

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