4-65605095-T-C

Variant names:

• chr4-65605095-T-C
• rs4404602
• NM_001281766.3:c.247-2791A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281766.3(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 NM_001281766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 8 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA5	NM_001281766.3	MANE Select	c.247-2791A>G		intron	N/A	NP_001268695.1	B7ZKW7
	EPHA5	NM_001281765.3		c.247-2791A>G		intron	N/A	NP_001268694.1	B7ZKJ3
	EPHA5	NM_004439.8		c.247-2791A>G		intron	N/A	NP_004430.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA5	ENST00000613740.5	TSL:1 MANE Select	c.247-2791A>G		intron	N/A	ENSP00000478537.1	B7ZKW7
	EPHA5	ENST00000622150.4	TSL:1	c.247-2791A>G		intron	N/A	ENSP00000480763.1	B7ZKJ3
	EPHA5	ENST00000273854.7	TSL:1	c.247-2791A>G		intron	N/A	ENSP00000273854.3	P54756-1

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

African (AFR) AF: 0.142 AC: 5885 AN: 41494

American (AMR) AF: 0.379 AC: 5791 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1182 AN: 3472

East Asian (EAS) AF: 0.562 AC: 2892 AN: 5150

South Asian (SAS) AF: 0.278 AC: 1336 AN: 4814

European-Finnish (FIN) AF: 0.272 AC: 2872 AN: 10572

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16491 AN: 67934

Other (OTH) AF: 0.275 AC: 581 AN: 2110

Alfa AF: 0.245 Hom.: 9156

Bravo AF: 0.254

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.35
PhyloP100		-0.45
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: rs4404602; hg19: chr4-66470813;