rs13316480

Positions:

• chr3-134959198-C-T

Variant summary

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

The NM_004441.5(EPHB1):​c.805+7146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,188 control chromosomes in the GnomAD database, including 1,106 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 0.11 (1106 hom., cov: 31)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.805+7146C>T		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+7146C>T		intron_variant		1	NM_004441.5	ENSP00000381097	P1
EPHB1	ENST00000482618.5	c.805+7146C>T		intron_variant, NMD_transcript_variant		1		ENSP00000420338
EPHB1	ENST00000488154.5	n.471+7480C>T		intron_variant, non_coding_transcript_variant		1
EPHB1	ENST00000647596.1	c.805+7146C>T		intron_variant				ENSP00000497153

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17321 AN: 152070 Hom.: 1104 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.114 AC: 17329 AN: 152188 Hom.: 1106 Cov.: 31 AF XY: 0.111 AC XY: 8294 AN XY: 74394

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0696

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0928

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.117 Hom.: 185

Bravo AF: 0.107

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.54

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: rs13316480; hg19: chr3-134678040;