chr4-65332086-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001281766.3(EPHA5):​c.2832G>T​(p.Gly944Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-0.041 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281766.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA5	NM_001281766.3	MANE Select	c.2832G>T	p.Gly944Gly	synonymous	Exon 16 of 17	NP_001268695.1
	EPHA5	NM_001281765.3		c.2898G>T	p.Gly966Gly	synonymous	Exon 17 of 18	NP_001268694.1
	EPHA5	NM_004439.8		c.2895G>T	p.Gly965Gly	synonymous	Exon 17 of 18	NP_004430.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA5	ENST00000613740.5	TSL:1 MANE Select	c.2832G>T	p.Gly944Gly	synonymous	Exon 16 of 17	ENSP00000478537.1
	EPHA5	ENST00000622150.4	TSL:1	c.2898G>T	p.Gly966Gly	synonymous	Exon 17 of 18	ENSP00000480763.1
	EPHA5	ENST00000273854.7	TSL:1	c.2895G>T	p.Gly965Gly	synonymous	Exon 17 of 18	ENSP00000273854.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 31828

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		-0.041

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: rs7349683; hg19: chr4-66197804;