4-65633298-T-G

Variant names:

• chr4-65633298-T-G
• rs11735820
• NM_001281766.3:c.246+10065A>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001281766.3(EPHA5):​c.246+10065A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,510 control chromosomes in the GnomAD database, including 8,037 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 0.32 (8037 hom., cov: 30)
• Consequence: EPHA5 NM_001281766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA5	NM_001281766.3	c.246+10065A>C		intron_variant	Intron 2 of 16	ENST00000613740.5	NP_001268695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA5	ENST00000613740.5	c.246+10065A>C		intron_variant	Intron 2 of 16	1	NM_001281766.3	ENSP00000478537.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48715 AN: 151392 Hom.: 8036 Cov.: 30

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.322 AC: 48734 AN: 151510 Hom.: 8037 Cov.: 30 AF XY: 0.322 AC XY: 23818 AN XY: 73998

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.291

Alfa AF: 0.310 Hom.: 2229

Bravo AF: 0.305

Asia WGS AF: 0.263 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.72

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: rs11735820; hg19: chr4-66499016;