3-134995934-G-C

Position:

• chr3-134995934-G-C

Variant summary

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

The NM_004441.5(EPHB1):​c.805+43882G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 150,410 control chromosomes in the GnomAD database, including 2,411 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 0.15 (2411 hom., cov: 33)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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]

EPHB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.805+43882G>C		intron_variant		ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.805+43882G>C		intron_variant		1	NM_004441.5	ENSP00000381097.3
EPHB1	ENST00000482618.5	n.*71+17857G>C		intron_variant		1		ENSP00000420338.1
EPHB1	ENST00000488154.5	n.471+44216G>C		intron_variant		1
EPHB1	ENST00000647596.1	c.805+43882G>C		intron_variant				ENSP00000497153.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22616 AN: 150294 Hom.: 2413 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0817

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.151 AC: 22644 AN: 150410 Hom.: 2411 Cov.: 33 AF XY: 0.151 AC XY: 11085 AN XY: 73436

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0821

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0530 Hom.: 57

Bravo AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.63

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: rs16842453; hg19: chr3-134714776;