NM_004441.5:c.1298-6543C>G

Variant names:

• chr3-135147609-C-G
• rs966513
• NM_004441.5:c.1298-6543C>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.1298-6543C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,182 control chromosomes in the GnomAD database, including 1,359 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 0.13 (1359 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.1298-6543C>G		intron_variant	Intron 5 of 15	ENST00000398015.8	NP_004432.1
LOC102724019	XR_427412.4	n.173+121G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.1298-6543C>G		intron_variant	Intron 5 of 15	1	NM_004441.5	ENSP00000381097.3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19336 AN: 152064 Hom.: 1360 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.127 AC: 19333 AN: 152182 Hom.: 1359 Cov.: 32 AF XY: 0.128 AC XY: 9529 AN XY: 74404

African (AFR) AF: 0.184 AC: 7632 AN: 41516

American (AMR) AF: 0.0951 AC: 1455 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 294 AN: 3466

East Asian (EAS) AF: 0.174 AC: 897 AN: 5166

South Asian (SAS) AF: 0.201 AC: 969 AN: 4816

European-Finnish (FIN) AF: 0.104 AC: 1101 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0972 AC: 6612 AN: 68000

Other (OTH) AF: 0.116 AC: 244 AN: 2110

Alfa AF: 0.0516 Hom.: 50

Bravo AF: 0.129

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.87
DANN	Benign	0.56
PhyloP100		-0.26
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: rs966513; hg19: chr3-134866451;