dbSNP rs10465543: EPHB2:c.811+22649G>A (chr1-22807725-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017449.5(EPHB2):c.811+22649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,234 control chromosomes in the GnomAD database, including 2,963 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 0.19 ( 2963 hom., cov: 33)

Consequence

EPHB2
NM_017449.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.788

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

bleeding disorder, platelet-type, 22
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

EPHB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB2	NM_017449.5 link	c.811+22649G>A		intron_variant	Intron 3 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.811+22649G>A		intron_variant	Intron 3 of 15	1	NM_017449.5	ENSP00000363761.3		P29323-2
EPHB2	ENST00000374627.1 link	c.793+22649G>A		intron_variant	Intron 3 of 14	5		ENSP00000363758.1		B1AKC9

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29631

AN:

152116

Hom.:

2967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.195

AC:

29623

AN:

152234

Hom.:

2963

Cov.:

AF XY:

0.196

AC XY:

14609

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.173

AC:

7182

AN:

41552

American (AMR)

AF:

0.232

AC:

3544

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

550

AN:

3470

East Asian (EAS)

AF:

0.183

AC:

949

AN:

5174

South Asian (SAS)

AF:

0.328

AC:

1579

AN:

4820

European-Finnish (FIN)

AF:

0.163

AC:

1725

AN:

10610

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13470

AN:

68008

Other (OTH)

AF:

0.180

AC:

380

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1232

2464

3697

4929

6161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.196

Hom.:

11261

Bravo

AF:

0.194

Asia WGS

AF:

0.236

AC:

823

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.70

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over