chr3-134796494-T-G

Position:

• chr3-134796494-T-G

Variant summary

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

The NM_004441.5(EPHB1):​c.58+805T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,236 control chromosomes in the GnomAD database, including 43,449 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 0.71 (43439 hom., cov: 34)
  • Exomes 𝑓: 0.86 (10 hom.)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.58+805T>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+805T>G		intron_variant		1	NM_004441.5	ENSP00000381097	P1
	ENST00000656103.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108271 AN: 152090 Hom.: 43451 Cov.: 34

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.857 AC: 24 AN: 28 Hom.: 10 AF XY: 0.875 AC XY: 21 AN XY: 24

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.750

Gnomad4 NFE exome AF: 0.950

GnomAD4 genome AF: 0.711 AC: 108270 AN: 152208 Hom.: 43439 Cov.: 34 AF XY: 0.713 AC XY: 53039 AN XY: 74426

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.764

Alfa AF: 0.825 Hom.: 40758

Bravo AF: 0.690

Asia WGS AF: 0.699 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.4
DANN	Benign	0.51

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: rs3732568; hg19: chr3-134515336;