rs4263970

chr1-22737437-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017449.5(EPHB2):c.61+26394T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,036 control chromosomes in the GnomAD database, including 23,870 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 0.55 (23870 hom., cov: 32)
• Consequence: EPHB2 NM_017449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHB2	NM_017449.5	c.61+26394T>C		intron_variant		ENST00000374630.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHB2	ENST00000374630.8	c.61+26394T>C		intron_variant		1	NM_017449.5	P4
EPHB2	ENST00000374632.7	c.61+26394T>C		intron_variant		1		A1
EPHB2	ENST00000400191.7	c.61+26394T>C		intron_variant		1
EPHB2	ENST00000544305.5	c.61+26394T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83851 AN: 151918 Hom.: 23825 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.552 AC: 83954 AN: 152036 Hom.: 23870 Cov.: 32 AF XY: 0.562 AC XY: 41817 AN XY: 74342

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.535

Alfa AF: 0.510 Hom.: 19188

Bravo AF: 0.554

Asia WGS AF: 0.801 AC: 2786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.7
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs4263970; hg19: chr1-23063930;