rs6782527

chr3-89393219-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005233.6(EPHA3):c.1307-2618C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,072 control chromosomes in the GnomAD database, including 3,583 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 0.19 (3583 hom., cov: 32)
• Consequence: EPHA3 NM_005233.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA3	NM_005233.6	c.1307-2618C>T		intron_variant		ENST00000336596.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA3	ENST00000336596.7	c.1307-2618C>T		intron_variant		1	NM_005233.6	P1
EPHA3	ENST00000452448.6	c.1307-2618C>T		intron_variant		1
EPHA3	ENST00000494014.1	c.1307-2618C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28910 AN: 151954 Hom.: 3583 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.190 AC: 28904 AN: 152072 Hom.: 3583 Cov.: 32 AF XY: 0.190 AC XY: 14125 AN XY: 74324

Gnomad4 AFR AF: 0.0480

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.164

Alfa AF: 0.243 Hom.: 2684

Bravo AF: 0.174

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
Cadd	Benign	20
Dann	Benign	0.74

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: rs6782527; hg19: chr3-89442369;