1-22740019-T-C

Variant names:

• chr1-22740019-T-C
• rs1318720
• NM_017449.5:c.61+28976T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017449.5(EPHB2):​c.61+28976T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,808 control chromosomes in the GnomAD database, including 19,033 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 0.48 (19033 hom., cov: 33)
• Consequence: EPHB2 NM_017449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB2	NM_017449.5	c.61+28976T>C		intron_variant	Intron 1 of 15	ENST00000374630.8	NP_059145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB2	ENST00000374630.8	c.61+28976T>C		intron_variant	Intron 1 of 15	1	NM_017449.5	ENSP00000363761.3
EPHB2	ENST00000400191.7	c.61+28976T>C		intron_variant	Intron 1 of 16	1		ENSP00000383053.3
EPHB2	ENST00000374632.7	c.61+28976T>C		intron_variant	Intron 1 of 15	1		ENSP00000363763.3
EPHB2	ENST00000544305.5	c.61+28976T>C		intron_variant	Intron 1 of 6	1		ENSP00000444174.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73169 AN: 151690 Hom.: 19002 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.482 AC: 73247 AN: 151808 Hom.: 19033 Cov.: 33 AF XY: 0.495 AC XY: 36669 AN XY: 74150

African (AFR) AF: 0.322 AC: 13335 AN: 41468

American (AMR) AF: 0.573 AC: 8733 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3468

East Asian (EAS) AF: 0.938 AC: 4810 AN: 5128

South Asian (SAS) AF: 0.718 AC: 3458 AN: 4818

European-Finnish (FIN) AF: 0.546 AC: 5735 AN: 10512

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.498 AC: 33824 AN: 67858

Other (OTH) AF: 0.489 AC: 1031 AN: 2110

Alfa AF: 0.483 Hom.: 2971

Bravo AF: 0.476

Asia WGS AF: 0.778 AC: 2704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.83
PhyloP100		1.7
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: rs1318720; hg19: chr1-23066512;