rs2030737

Variant names:

• chr3-135090535-C-T
• rs2030737
• NM_004441.5:c.806-15913C>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.806-15913C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,136 control chromosomes in the GnomAD database, including 15,777 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 0.44 (15777 hom., cov: 34)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.806-15913C>T		intron_variant	Intron 3 of 15	ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.806-15913C>T		intron_variant	Intron 3 of 15	1	NM_004441.5	ENSP00000381097.3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67261 AN: 152018 Hom.: 15770 Cov.: 34

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.442 AC: 67262 AN: 152136 Hom.: 15777 Cov.: 34 AF XY: 0.438 AC XY: 32560 AN XY: 74372

African (AFR) AF: 0.321 AC: 13313 AN: 41498

American (AMR) AF: 0.450 AC: 6882 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1769 AN: 3470

East Asian (EAS) AF: 0.179 AC: 927 AN: 5172

South Asian (SAS) AF: 0.491 AC: 2362 AN: 4812

European-Finnish (FIN) AF: 0.424 AC: 4482 AN: 10574

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35942 AN: 67992

Other (OTH) AF: 0.454 AC: 961 AN: 2116

Alfa AF: 0.490 Hom.: 13118

Bravo AF: 0.438

Asia WGS AF: 0.341 AC: 1190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.90
DANN	Benign	0.87
PhyloP100		-0.91
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: rs2030737; hg19: chr3-134809377;