rs9836340

Positions:

• chr3-89356604-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005233.6(EPHA3):​c.1306+14514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 150,804 control chromosomes in the GnomAD database, including 9,480 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 0.32 (9480 hom., cov: 30)
• Consequence: EPHA3 NM_005233.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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

Verdict is Benign. Variant got -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 = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA3	NM_005233.6	c.1306+14514A>G		intron_variant		ENST00000336596.7	NP_005224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA3	ENST00000336596.7	c.1306+14514A>G		intron_variant		1	NM_005233.6	ENSP00000337451.2
EPHA3	ENST00000494014.1	c.1306+14514A>G		intron_variant		1		ENSP00000419190.1
EPHA3	ENST00000452448.6	c.1306+14514A>G		intron_variant		1		ENSP00000399926.2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48213 AN: 150684 Hom.: 9463 Cov.: 30

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.0852

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.320 AC: 48259 AN: 150804 Hom.: 9480 Cov.: 30 AF XY: 0.315 AC XY: 23225 AN XY: 73648

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0953

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.273

Alfa AF: 0.281 Hom.: 8592

Bravo AF: 0.319

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs9836340; hg19: chr3-89405754;