NM_004441.5:c.805+43882G>C

Variant names:

• chr3-134995934-G-C
• rs16842453
• NM_004441.5:c.805+43882G>C

Variant summary

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

The NM_004441.5(EPHB1):​c.805+43882G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 150,410 control chromosomes in the GnomAD database, including 2,411 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 0.15 (2411 hom., cov: 33)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004441.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB1	NM_004441.5	MANE Select	c.805+43882G>C		intron	N/A	NP_004432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB1	ENST00000398015.8	TSL:1 MANE Select	c.805+43882G>C		intron	N/A	ENSP00000381097.3
	EPHB1	ENST00000482618.5	TSL:1	n.*71+17857G>C		intron	N/A	ENSP00000420338.1
	EPHB1	ENST00000488154.5	TSL:1	n.471+44216G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22616 AN: 150294 Hom.: 2413 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0817

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.151 AC: 22644 AN: 150410 Hom.: 2411 Cov.: 33 AF XY: 0.151 AC XY: 11085 AN XY: 73436

African (AFR) AF: 0.299 AC: 12188 AN: 40760

American (AMR) AF: 0.103 AC: 1557 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 253 AN: 3456

East Asian (EAS) AF: 0.105 AC: 545 AN: 5180

South Asian (SAS) AF: 0.166 AC: 798 AN: 4798

European-Finnish (FIN) AF: 0.139 AC: 1436 AN: 10332

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0821 AC: 5542 AN: 67510

Other (OTH) AF: 0.110 AC: 228 AN: 2074

Alfa AF: 0.0530 Hom.: 57

Bravo AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		0.044
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: rs16842453; hg19: chr3-134714776;