rs10465531

Variant names:

• chr1-22807299-G-A
• rs10465531
• NM_017449.5:c.811+22223G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017449.5(EPHB2):​c.811+22223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,058 control chromosomes in the GnomAD database, including 2,945 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 (2945 hom., cov: 32)
• Consequence: EPHB2 NM_017449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 1 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB2	NM_017449.5	c.811+22223G>A		intron_variant	Intron 3 of 15	ENST00000374630.8	NP_059145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB2	ENST00000374630.8	c.811+22223G>A		intron_variant	Intron 3 of 15	1	NM_017449.5	ENSP00000363761.3
EPHB2	ENST00000374627.1	c.793+22223G>A		intron_variant	Intron 3 of 14	5		ENSP00000363758.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29561 AN: 151940 Hom.: 2949 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.194 AC: 29553 AN: 152058 Hom.: 2945 Cov.: 32 AF XY: 0.196 AC XY: 14562 AN XY: 74326

African (AFR) AF: 0.173 AC: 7164 AN: 41482

American (AMR) AF: 0.234 AC: 3581 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3466

East Asian (EAS) AF: 0.184 AC: 952 AN: 5164

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4810

European-Finnish (FIN) AF: 0.162 AC: 1712 AN: 10554

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13436 AN: 67986

Other (OTH) AF: 0.179 AC: 377 AN: 2112

Alfa AF: 0.193 Hom.: 1415

Bravo AF: 0.195

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.72
PhyloP100		-0.053
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10465531; hg19: chr1-23133792;