3-89226756-T-C

Variant names:

• chr3-89226756-T-C
• rs9310117
• NM_005233.6:c.814+16236T>C

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+16236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,850 control chromosomes in the GnomAD database, including 19,314 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 0.49 (19314 hom., cov: 32)
• Consequence: EPHA3 NM_005233.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 4 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA3	NM_005233.6	c.814+16236T>C		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+16236T>C		intron_variant	Intron 3 of 16	1	NM_005233.6	ENSP00000337451.2
EPHA3	ENST00000494014.1	c.814+16236T>C		intron_variant	Intron 3 of 16	1		ENSP00000419190.1
EPHA3	ENST00000452448.6	c.814+16236T>C		intron_variant	Intron 3 of 6	1		ENSP00000399926.2

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73816 AN: 151732 Hom.: 19311 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.486 AC: 73833 AN: 151850 Hom.: 19314 Cov.: 32 AF XY: 0.490 AC XY: 36351 AN XY: 74172

African (AFR) AF: 0.286 AC: 11872 AN: 41468

American (AMR) AF: 0.602 AC: 9162 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2098 AN: 3462

East Asian (EAS) AF: 0.689 AC: 3554 AN: 5158

South Asian (SAS) AF: 0.673 AC: 3238 AN: 4814

European-Finnish (FIN) AF: 0.475 AC: 5009 AN: 10550

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 36982 AN: 67876

Other (OTH) AF: 0.519 AC: 1096 AN: 2110

Alfa AF: 0.499 Hom.: 2738

Bravo AF: 0.485

Asia WGS AF: 0.638 AC: 2217 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		0.18
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: rs9310117; hg19: chr3-89275906;