1-22811138-C-T

Variant names:

• chr1-22811138-C-T
• rs4655117
• NM_017449.5:c.811+26062C>T

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+26062C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,936 control chromosomes in the GnomAD database, including 7,725 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 0.30 (7725 hom., cov: 31)
• Consequence: EPHB2 NM_017449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017449.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB2	NM_017449.5	MANE Select	c.811+26062C>T		intron	N/A	NP_059145.2
	EPHB2	NM_001309193.2		c.811+26062C>T		intron	N/A	NP_001296122.1
	EPHB2	NM_004442.7		c.811+26062C>T		intron	N/A	NP_004433.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB2	ENST00000374630.8	TSL:1 MANE Select	c.811+26062C>T		intron	N/A	ENSP00000363761.3
	EPHB2	ENST00000400191.7	TSL:1	c.811+26062C>T		intron	N/A	ENSP00000383053.3
	EPHB2	ENST00000374632.7	TSL:1	c.811+26062C>T		intron	N/A	ENSP00000363763.3

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45829 AN: 151818 Hom.: 7727 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.302 AC: 45835 AN: 151936 Hom.: 7725 Cov.: 31 AF XY: 0.310 AC XY: 23046 AN XY: 74252

African (AFR) AF: 0.214 AC: 8840 AN: 41402

American (AMR) AF: 0.380 AC: 5802 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3470

East Asian (EAS) AF: 0.743 AC: 3840 AN: 5170

South Asian (SAS) AF: 0.490 AC: 2354 AN: 4802

European-Finnish (FIN) AF: 0.284 AC: 2994 AN: 10554

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19975 AN: 67946

Other (OTH) AF: 0.291 AC: 615 AN: 2112

Alfa AF: 0.287 Hom.: 1194

Bravo AF: 0.303

Asia WGS AF: 0.533 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.41
PhyloP100		0.16
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: rs4655117; hg19: chr1-23137631;