rs6797260

Positions:

• chr3-89253336-A-T

Variant summary

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

The NM_005233.6(EPHA3):​c.814+42816A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,994 control chromosomes in the GnomAD database, including 7,263 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 0.28 (7263 hom., cov: 31)
• Consequence: EPHA3 NM_005233.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA3	NM_005233.6	c.814+42816A>T		intron_variant		ENST00000336596.7	NP_005224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA3	ENST00000336596.7	c.814+42816A>T		intron_variant		1	NM_005233.6	ENSP00000337451	P1
EPHA3	ENST00000452448.6	c.814+42816A>T		intron_variant		1		ENSP00000399926
EPHA3	ENST00000494014.1	c.814+42816A>T		intron_variant		1		ENSP00000419190

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41854 AN: 151876 Hom.: 7253 Cov.: 31

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.276 AC: 41877 AN: 151994 Hom.: 7263 Cov.: 31 AF XY: 0.280 AC XY: 20785 AN XY: 74260

Gnomad4 AFR AF: 0.0677

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.310

Alfa AF: 0.290 Hom.: 903

Bravo AF: 0.277

Asia WGS AF: 0.412 AC: 1430 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.77

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: rs6797260; hg19: chr3-89302486;