chr3-134951123-G-A

Position:

• chr3-134951123-G-A

Variant summary

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

The NM_004441.5(EPHB1):​c.124-248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,002 control chromosomes in the GnomAD database, including 19,694 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 0.50 (19694 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479

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 (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.124-248G>A		intron_variant		ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.124-248G>A		intron_variant		1	NM_004441.5	ENSP00000381097	P1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75540 AN: 151884 Hom.: 19678 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.497 AC: 75601 AN: 152002 Hom.: 19694 Cov.: 32 AF XY: 0.491 AC XY: 36466 AN XY: 74302

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.512

Alfa AF: 0.475 Hom.: 2182

Bravo AF: 0.516

Asia WGS AF: 0.433 AC: 1507 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	4.6
DANN	Benign	0.39

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: rs11929692; hg19: chr3-134669965;