rs9844754

Positions:

• chr3-134815561-A-G
• chr3-134815561-A-T

Variant summary

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

The NM_004441.5(EPHB1):​c.58+19872A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,062 control chromosomes in the GnomAD database, including 32,601 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 0.64 (32601 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.58+19872A>G		intron_variant		ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.58+19872A>G		intron_variant		1	NM_004441.5	ENSP00000381097	P1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97073 AN: 151942 Hom.: 32601 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.639 AC: 97120 AN: 152062 Hom.: 32601 Cov.: 32 AF XY: 0.643 AC XY: 47800 AN XY: 74336

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.648

Alfa AF: 0.679 Hom.: 4533

Bravo AF: 0.630

Asia WGS AF: 0.650 AC: 2261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.19
DANN	Benign	0.36

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: rs9844754; hg19: chr3-134534403;