rs7678888

Positions:

• chr4-65332341-G-A
• chr4-65332341-G-C
• chr4-65332341-G-T

Variant summary

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

The NM_001281766.3(EPHA5):​c.2790-213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,504 control chromosomes in the GnomAD database, including 27,279 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 0.58 (27279 hom., cov: 31)
• Consequence: EPHA5 NM_001281766.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA5	NM_001281766.3	c.2790-213C>T		intron_variant		ENST00000613740.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA5	ENST00000613740.5	c.2790-213C>T		intron_variant		1	NM_001281766.3	A2

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87822 AN: 151386 Hom.: 27262 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.580 AC: 87874 AN: 151504 Hom.: 27279 Cov.: 31 AF XY: 0.582 AC XY: 43062 AN XY: 73990

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.623

Alfa AF: 0.659 Hom.: 18940

Bravo AF: 0.562

Asia WGS AF: 0.657 AC: 2280 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.25

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: rs7678888; hg19: chr4-66198059;