rs1515366

chr3-134873468-T-A

Variant summary

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

The NM_004441.5(EPHB1):c.59-52348T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,126 control chromosomes in the GnomAD database, including 9,394 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 0.35 (9394 hom., cov: 33)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

Genes affected

EPHB1 (HGNC:3392): (EPH receptor B1) Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene is a receptor for ephrin-B family members. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHB1	NM_004441.5	c.59-52348T>A		intron_variant		ENST00000398015.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHB1	ENST00000398015.8	c.59-52348T>A		intron_variant		1	NM_004441.5	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53132 AN: 152010 Hom.: 9394 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.349 AC: 53166 AN: 152126 Hom.: 9394 Cov.: 33 AF XY: 0.350 AC XY: 26025 AN XY: 74388

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.358

Alfa AF: 0.336 Hom.: 1049

Bravo AF: 0.347

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.2
Dann	Benign	0.86

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: rs1515366; hg19: chr3-134592310;