rs11716850

Variant names:

• chr3-135248122-C-T
• rs11716850
• NM_004441.5:c.2497-194C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004441.5(EPHB1):​c.2497-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,162 control chromosomes in the GnomAD database, including 2,300 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 0.16 (2300 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 1 publications found

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]

ENSG00000240086 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.2497-194C>T		intron_variant	Intron 13 of 15	ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.2497-194C>T		intron_variant	Intron 13 of 15	1	NM_004441.5	ENSP00000381097.3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25054 AN: 152044 Hom.: 2290 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.165 AC: 25087 AN: 152162 Hom.: 2300 Cov.: 32 AF XY: 0.174 AC XY: 12977 AN XY: 74372

African (AFR) AF: 0.144 AC: 5966 AN: 41534

American (AMR) AF: 0.147 AC: 2244 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1527 AN: 5150

South Asian (SAS) AF: 0.301 AC: 1450 AN: 4810

European-Finnish (FIN) AF: 0.267 AC: 2825 AN: 10580

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10137 AN: 68002

Other (OTH) AF: 0.137 AC: 290 AN: 2110

Alfa AF: 0.158 Hom.: 254

Bravo AF: 0.153

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.63
PhyloP100		0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11716850; hg19: chr3-134966964;