rs4612601

Positions:

• chr1-22740551-G-A

Variant summary

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

The NM_017449.5(EPHB2):​c.61+29508G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,998 control chromosomes in the GnomAD database, including 22,742 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 0.54 (22742 hom., cov: 32)
• Consequence: EPHB2 NM_017449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB2	NM_017449.5	c.61+29508G>A		intron_variant		ENST00000374630.8	NP_059145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHB2	ENST00000374630.8	c.61+29508G>A		intron_variant		1	NM_017449.5	ENSP00000363761.3
EPHB2	ENST00000400191.7	c.61+29508G>A		intron_variant		1		ENSP00000383053.3
EPHB2	ENST00000374632.7	c.61+29508G>A		intron_variant		1		ENSP00000363763.3
EPHB2	ENST00000544305.5	c.61+29508G>A		intron_variant		1		ENSP00000444174.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81846 AN: 151878 Hom.: 22701 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.539 AC: 81944 AN: 151998 Hom.: 22742 Cov.: 32 AF XY: 0.550 AC XY: 40835 AN XY: 74288

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.525

Alfa AF: 0.519 Hom.: 11057

Bravo AF: 0.540

Asia WGS AF: 0.788 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.55

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: rs4612601; hg19: chr1-23067044;