3-134872296-C-T

Variant names:

• chr3-134872296-C-T
• rs6762261
• NM_004441.5:c.59-53520C>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.59-53520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,154 control chromosomes in the GnomAD database, including 2,883 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 0.19 (2883 hom., cov: 33)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 2 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]

ENSG00000288700 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.59-53520C>T		intron_variant	Intron 1 of 15	ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.59-53520C>T		intron_variant	Intron 1 of 15	1	NM_004441.5	ENSP00000381097.3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28576 AN: 152036 Hom.: 2885 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.188 AC: 28596 AN: 152154 Hom.: 2883 Cov.: 33 AF XY: 0.186 AC XY: 13866 AN XY: 74404

African (AFR) AF: 0.243 AC: 10067 AN: 41476

American (AMR) AF: 0.178 AC: 2714 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3472

East Asian (EAS) AF: 0.0986 AC: 511 AN: 5180

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4816

European-Finnish (FIN) AF: 0.140 AC: 1488 AN: 10610

Middle Eastern (MID) AF: 0.245 AC: 71 AN: 290

European-Non Finnish (NFE) AF: 0.166 AC: 11312 AN: 67998

Other (OTH) AF: 0.183 AC: 387 AN: 2112

Alfa AF: 0.170 Hom.: 3859

Bravo AF: 0.190

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	-0.91
CADD	Benign	0.65
DANN	Benign	0.57
PhyloP100		-0.47
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: rs6762261; hg19: chr3-134591138;