rs3821502

Variant names:

• chr3-135193725-A-G
• rs3821502
• NM_004441.5:c.2130+902A>G

Variant summary

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

The NM_004441.5(EPHB1):​c.2130+902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,146 control chromosomes in the GnomAD database, including 11,207 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 0.37 (11207 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.2130+902A>G		intron_variant	Intron 11 of 15	ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.2130+902A>G		intron_variant	Intron 11 of 15	1	NM_004441.5	ENSP00000381097.3
EPHB1	ENST00000647596.1	c.2130+902A>G		intron_variant	Intron 11 of 15			ENSP00000497153.1
EPHB1	ENST00000493838.1	c.813+902A>G		intron_variant	Intron 9 of 13	2		ENSP00000419574.1
ENSG00000240086	ENST00000649588.1	n.329-35397T>C		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56611 AN: 152028 Hom.: 11213 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.372 AC: 56638 AN: 152146 Hom.: 11207 Cov.: 32 AF XY: 0.378 AC XY: 28106 AN XY: 74386

African (AFR) AF: 0.271 AC: 11242 AN: 41524

American (AMR) AF: 0.443 AC: 6777 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3466

East Asian (EAS) AF: 0.632 AC: 3270 AN: 5172

South Asian (SAS) AF: 0.523 AC: 2517 AN: 4816

European-Finnish (FIN) AF: 0.334 AC: 3541 AN: 10592

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26969 AN: 67976

Other (OTH) AF: 0.371 AC: 783 AN: 2110

Alfa AF: 0.380 Hom.: 14634

Bravo AF: 0.371

Asia WGS AF: 0.555 AC: 1926 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.74
PhyloP100		-0.20
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: rs3821502; hg19: chr3-134912567;