rs870898

Variant names:

• chr3-89367914-C-T
• rs870898
• NM_005233.6:c.1306+25824C>T

Variant summary

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

The NM_005233.6(EPHA3):​c.1306+25824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 150,236 control chromosomes in the GnomAD database, including 6,414 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 0.27 (6414 hom., cov: 32)
• Consequence: EPHA3 NM_005233.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773
• Publications: 5 publications found

Genes affected

EPHA3 (HGNC:3387): (EPH receptor A3) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin 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. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005233.6. 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
	EPHA3	NM_005233.6	MANE Select	c.1306+25824C>T		intron	N/A	NP_005224.2
	EPHA3	NM_001410778.1		c.1306+25824C>T		intron	N/A	NP_001397707.1
	EPHA3	NM_182644.3		c.1306+25824C>T		intron	N/A	NP_872585.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA3	ENST00000336596.7	TSL:1 MANE Select	c.1306+25824C>T		intron	N/A	ENSP00000337451.2
	EPHA3	ENST00000494014.1	TSL:1	c.1306+25824C>T		intron	N/A	ENSP00000419190.1
	EPHA3	ENST00000452448.6	TSL:1	c.1306+25824C>T		intron	N/A	ENSP00000399926.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 39818 AN: 150116 Hom.: 6409 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.265 AC: 39847 AN: 150236 Hom.: 6414 Cov.: 32 AF XY: 0.263 AC XY: 19267 AN XY: 73378

African (AFR) AF: 0.278 AC: 11460 AN: 41232

American (AMR) AF: 0.225 AC: 3365 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 519 AN: 3444

East Asian (EAS) AF: 0.102 AC: 521 AN: 5118

South Asian (SAS) AF: 0.0935 AC: 449 AN: 4804

European-Finnish (FIN) AF: 0.376 AC: 3917 AN: 10406

Middle Eastern (MID) AF: 0.116 AC: 33 AN: 284

European-Non Finnish (NFE) AF: 0.284 AC: 19029 AN: 66994

Other (OTH) AF: 0.231 AC: 475 AN: 2056

Alfa AF: 0.268 Hom.: 8811

Bravo AF: 0.257

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.36
PhyloP100		-0.77
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: rs870898; hg19: chr3-89417064;