rs9832305

Positions:

• chr3-89343628-T-C

Variant summary

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

The NM_005233.6(EPHA3):​c.1306+1538T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,134 control chromosomes in the GnomAD database, including 8,262 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 0.31 (8262 hom., cov: 32)
• Consequence: EPHA3 NM_005233.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490

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	UniProt
EPHA3	NM_005233.6	c.1306+1538T>C		intron_variant		ENST00000336596.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA3	ENST00000336596.7	c.1306+1538T>C		intron_variant		1	NM_005233.6	P1
EPHA3	ENST00000452448.6	c.1306+1538T>C		intron_variant		1
EPHA3	ENST00000494014.1	c.1306+1538T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47477 AN: 152014 Hom.: 8249 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.312 AC: 47519 AN: 152134 Hom.: 8262 Cov.: 32 AF XY: 0.309 AC XY: 22987 AN XY: 74384

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.259

Alfa AF: 0.274 Hom.: 2920

Bravo AF: 0.311

Asia WGS AF: 0.113 AC: 391 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	0.41
DANN	Benign	0.67

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: rs9832305; hg19: chr3-89392778;