4-65332086-C-T

Position:

• chr4-65332086-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001281766.3(EPHA5):​c.2832G>A​(p.Gly944Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,608,188 control chromosomes in the GnomAD database, including 100,908 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 0.29 (7424 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93484 hom.)
• Consequence: EPHA5 NM_001281766.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

Genes affected

EPHA5 (HGNC:3389): (EPH receptor A5) 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. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-0.041 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA5	NM_001281766.3	c.2832G>A	p.Gly944Gly	synonymous_variant	16/17	ENST00000613740.5	NP_001268695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA5	ENST00000613740.5	c.2832G>A	p.Gly944Gly	synonymous_variant	16/17	1	NM_001281766.3	ENSP00000478537.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44524 AN: 151444 Hom.: 7409 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.297

GnomAD3 exomes AF: 0.346 AC: 86178 AN: 249414 Hom.: 15584 AF XY: 0.355 AC XY: 47897 AN XY: 134914

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.422

Gnomad SAS exome AF: 0.431

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.354 AC: 515808 AN: 1456626 Hom.: 93484 Cov.: 33 AF XY: 0.357 AC XY: 258728 AN XY: 724798

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.294 AC: 44559 AN: 151562 Hom.: 7424 Cov.: 32 AF XY: 0.297 AC XY: 21978 AN XY: 74026

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.303

Alfa AF: 0.338 Hom.: 16545

Bravo AF: 0.278

Asia WGS AF: 0.411 AC: 1434 AN: 3478

EpiCase AF: 0.353

EpiControl AF: 0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.1
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7349683; hg19: chr4-66197804; COSMIC: COSV56661916;