rs36059

Positions:

• chr3-135013890-C-A
• chr3-135013890-C-G

Variant summary

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

The NM_004441.5(EPHB1):​c.805+61838C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,958 control chromosomes in the GnomAD database, including 11,058 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 0.34 (11058 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

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 = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHB1	NM_004441.5	c.805+61838C>A		intron_variant		ENST00000398015.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHB1	ENST00000398015.8	c.805+61838C>A		intron_variant		1	NM_004441.5	P1
EPHB1	ENST00000482618.5	c.*71+35813C>A		intron_variant, NMD_transcript_variant		1
EPHB1	ENST00000488154.5	n.471+62172C>A		intron_variant, non_coding_transcript_variant		1
EPHB1	ENST00000647596.1	c.805+61838C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51535 AN: 151840 Hom.: 11036 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.340 AC: 51614 AN: 151958 Hom.: 11058 Cov.: 32 AF XY: 0.335 AC XY: 24884 AN XY: 74260

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.282

Alfa AF: 0.247 Hom.: 6986

Bravo AF: 0.347

Asia WGS AF: 0.213 AC: 742 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	1.2
DANN	Benign	0.43

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: rs36059; hg19: chr3-134732732;