rs3799816

Positions:

• chr6-93253683-C-T

Variant summary

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

The NM_004440.4(EPHA7):​c.2532+964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,792 control chromosomes in the GnomAD database, including 15,718 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 0.44 (15718 hom., cov: 31)
• Consequence: EPHA7 NM_004440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

Genes affected

EPHA7 (HGNC:3390): (EPH receptor A7) 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. Increased expression of this gene is associated with multiple forms of carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA7	NM_004440.4	c.2532+964G>A		intron_variant		ENST00000369303.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA7	ENST00000369303.9	c.2532+964G>A		intron_variant		1	NM_004440.4	P3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67074 AN: 151674 Hom.: 15727 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.442 AC: 67062 AN: 151792 Hom.: 15718 Cov.: 31 AF XY: 0.450 AC XY: 33340 AN XY: 74164

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.470

Alfa AF: 0.463 Hom.: 4161

Bravo AF: 0.432

Asia WGS AF: 0.628 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6
DANN	Benign	0.63

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: rs3799816; hg19: chr6-93963401;