4-65332086-C-T

Variant names:

• chr4-65332086-C-T
• rs7349683
• NM_001281766.3:c.2832G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 51 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPHA5	NM_001281766.3	c.2832G>A	p.Gly944Gly	synonymous_variant	Exon 16 of 17	ENST00000613740.5	NP_001268695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA5	ENST00000613740.5	c.2832G>A	p.Gly944Gly	synonymous_variant	Exon 16 of 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

GnomAD2 exomes AF: 0.346 AC: 86178 AN: 249414 AF XY: 0.355

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 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

African (AFR) AF: 0.119 AC: 3967 AN: 33244

American (AMR) AF: 0.296 AC: 13133 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 8940 AN: 25986

East Asian (EAS) AF: 0.435 AC: 17218 AN: 39610

South Asian (SAS) AF: 0.426 AC: 36658 AN: 85988

European-Finnish (FIN) AF: 0.351 AC: 18700 AN: 53316

Middle Eastern (MID) AF: 0.350 AC: 2007 AN: 5740

European-Non Finnish (NFE) AF: 0.356 AC: 394581 AN: 1108322

Other (OTH) AF: 0.343 AC: 20604 AN: 60108

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

African (AFR) AF: 0.127 AC: 5249 AN: 41412

American (AMR) AF: 0.298 AC: 4516 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1252 AN: 3456

East Asian (EAS) AF: 0.435 AC: 2219 AN: 5106

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4822

European-Finnish (FIN) AF: 0.350 AC: 3691 AN: 10548

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24418 AN: 67754

Other (OTH) AF: 0.303 AC: 638 AN: 2104

Alfa AF: 0.333 Hom.: 31828

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
PhyloP100		-0.041
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7349683; hg19: chr4-66197804; COSMIC: COSV56661916;