1-22828738-A-G

Variant names:

• chr1-22828738-A-G
• rs12090415
• NM_017449.5:c.812-34299A>G

Variant summary

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

The NM_017449.5(EPHB2):​c.812-34299A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,096 control chromosomes in the GnomAD database, including 23,663 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 0.56 (23663 hom., cov: 33)
• Consequence: EPHB2 NM_017449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB2	NM_017449.5	c.812-34299A>G		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.812-34299A>G		intron_variant	Intron 3 of 15	1	NM_017449.5	ENSP00000363761.3
EPHB2	ENST00000374627.1	c.794-34299A>G		intron_variant	Intron 3 of 14	5		ENSP00000363758.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84530 AN: 151978 Hom.: 23644 Cov.: 33

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.556 AC: 84583 AN: 152096 Hom.: 23663 Cov.: 33 AF XY: 0.556 AC XY: 41367 AN XY: 74372

African (AFR) AF: 0.591 AC: 24532 AN: 41484

American (AMR) AF: 0.525 AC: 8028 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2236 AN: 3470

East Asian (EAS) AF: 0.704 AC: 3632 AN: 5160

South Asian (SAS) AF: 0.452 AC: 2177 AN: 4820

European-Finnish (FIN) AF: 0.552 AC: 5844 AN: 10580

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36412 AN: 67976

Other (OTH) AF: 0.574 AC: 1214 AN: 2114

Alfa AF: 0.547 Hom.: 39664

Bravo AF: 0.559

Asia WGS AF: 0.570 AC: 1980 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	4.0
DANN	Benign	0.57
PhyloP100		-0.035
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: rs12090415; hg19: chr1-23155231;