NM_004441.5:c.124-248G>A

Variant names:

• chr3-134951123-G-A
• rs11929692
• NM_004441.5:c.124-248G>A

Variant summary

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

The NM_004441.5(EPHB1):​c.124-248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,002 control chromosomes in the GnomAD database, including 19,694 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 0.50 (19694 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• 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]

ENSG00000288700 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 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.124-248G>A		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.124-248G>A		intron	N/A	ENSP00000381097.3
	EPHB1	ENST00000482618.5	TSL:1	n.124-248G>A		intron	N/A	ENSP00000420338.1
	EPHB1	ENST00000488154.5	TSL:1	n.124-248G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75540 AN: 151884 Hom.: 19678 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.497 AC: 75601 AN: 152002 Hom.: 19694 Cov.: 32 AF XY: 0.491 AC XY: 36466 AN XY: 74302

African (AFR) AF: 0.636 AC: 26375 AN: 41444

American (AMR) AF: 0.521 AC: 7962 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1027 AN: 5170

South Asian (SAS) AF: 0.520 AC: 2503 AN: 4812

European-Finnish (FIN) AF: 0.343 AC: 3623 AN: 10552

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30655 AN: 67968

Other (OTH) AF: 0.512 AC: 1077 AN: 2104

Alfa AF: 0.482 Hom.: 2346

Bravo AF: 0.516

Asia WGS AF: 0.433 AC: 1507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.39
PhyloP100		-0.48
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: rs11929692; hg19: chr3-134669965; COSMIC: COSV107504064;