rs4404602

Positions:

• chr4-65605095-T-C
• chr4-65605095-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000613740.5(EPHA5):​c.247-2791A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,020 control chromosomes in the GnomAD database, including 5,251 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 0.24 (5251 hom., cov: 31)
• Consequence: EPHA5 ENST00000613740.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA5	NM_001281766.3	c.247-2791A>G		intron_variant		ENST00000613740.5	NP_001268695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA5	ENST00000613740.5	c.247-2791A>G		intron_variant		1	NM_001281766.3	ENSP00000478537	A2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37174 AN: 151902 Hom.: 5232 Cov.: 31

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.245 AC: 37210 AN: 152020 Hom.: 5251 Cov.: 31 AF XY: 0.251 AC XY: 18623 AN XY: 74312

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.275

Alfa AF: 0.243 Hom.: 4155

Bravo AF: 0.254

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.35

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: rs4404602; hg19: chr4-66470813;