rs6797260

Variant names:

• chr3-89253336-A-T
• rs6797260
• NM_005233.6:c.814+42816A>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.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
• 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=-0.79).
• 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 rank	MANE	Protein	UniProt
EPHA3	NM_005233.6	c.814+42816A>T		intron_variant	Intron 3 of 16	ENST00000336596.7	NP_005224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA3	ENST00000336596.7	c.814+42816A>T		intron_variant	Intron 3 of 16	1	NM_005233.6	ENSP00000337451.2
EPHA3	ENST00000494014.1	c.814+42816A>T		intron_variant	Intron 3 of 16	1		ENSP00000419190.1
EPHA3	ENST00000452448.6	c.814+42816A>T		intron_variant	Intron 3 of 6	1		ENSP00000399926.2

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

African (AFR) AF: 0.0677 AC: 2810 AN: 41522

American (AMR) AF: 0.419 AC: 6387 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 973 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2305 AN: 5150

South Asian (SAS) AF: 0.409 AC: 1970 AN: 4820

European-Finnish (FIN) AF: 0.282 AC: 2973 AN: 10532

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23209 AN: 67934

Other (OTH) AF: 0.310 AC: 656 AN: 2114

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
PhyloP100		1.0
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: rs6797260; hg19: chr3-89302486;