rs6766459

Positions:

• chr3-135197201-G-T

Variant summary

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

The NM_004441.5(EPHB1):​c.2131-4273G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,054 control chromosomes in the GnomAD database, including 36,517 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 0.69 (36517 hom., cov: 33)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHB1	NM_004441.5	c.2131-4273G>T		intron_variant		ENST00000398015.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHB1	ENST00000398015.8	c.2131-4273G>T		intron_variant		1	NM_004441.5	P1
	ENST00000649588.1	n.329-38873C>A		intron_variant, non_coding_transcript_variant
EPHB1	ENST00000493838.1	c.814-4273G>T		intron_variant		2
EPHB1	ENST00000647596.1	c.2131-4273G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104461 AN: 151936 Hom.: 36486 Cov.: 33

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.688 AC: 104548 AN: 152054 Hom.: 36517 Cov.: 33 AF XY: 0.689 AC XY: 51182 AN XY: 74302

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.670

Alfa AF: 0.639 Hom.: 39035

Bravo AF: 0.696

Asia WGS AF: 0.666 AC: 2317 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.53

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: rs6766459; hg19: chr3-134916043;