3-135214774-C-T

Variant names:

• chr3-135214774-C-T
• rs4309752
• NM_004441.5:c.2346+13085C>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.2346+13085C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,050 control chromosomes in the GnomAD database, including 7,128 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 0.30 (7128 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.2346+13085C>T		intron_variant	Intron 12 of 15	ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.2346+13085C>T		intron_variant	Intron 12 of 15	1	NM_004441.5	ENSP00000381097.3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46025 AN: 151930 Hom.: 7117 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.303 AC: 46074 AN: 152050 Hom.: 7128 Cov.: 32 AF XY: 0.304 AC XY: 22600 AN XY: 74298

African (AFR) AF: 0.266 AC: 11045 AN: 41468

American (AMR) AF: 0.275 AC: 4207 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1105 AN: 3466

East Asian (EAS) AF: 0.209 AC: 1080 AN: 5176

South Asian (SAS) AF: 0.275 AC: 1323 AN: 4816

European-Finnish (FIN) AF: 0.374 AC: 3943 AN: 10556

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22396 AN: 67972

Other (OTH) AF: 0.290 AC: 612 AN: 2112

Alfa AF: 0.317 Hom.: 24534

Bravo AF: 0.296

Asia WGS AF: 0.227 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.6
DANN	Benign	0.72
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

Publications

LitVar

Other links and lift over

dbSNP: rs4309752; hg19: chr3-134933616;