rs2006999

Positions:

• chr6-93372290-A-G

Variant summary

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

The NM_004440.4(EPHA7):​c.833-13879T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,054 control chromosomes in the GnomAD database, including 3,104 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 0.18 (3104 hom., cov: 32)
• Consequence: EPHA7 NM_004440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA7	NM_004440.4	c.833-13879T>C		intron_variant		ENST00000369303.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA7	ENST00000369303.9	c.833-13879T>C		intron_variant		1	NM_004440.4	P3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27569 AN: 151936 Hom.: 3108 Cov.: 32

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0699

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.181 AC: 27560 AN: 152054 Hom.: 3104 Cov.: 32 AF XY: 0.178 AC XY: 13251 AN XY: 74330

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.0700

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.176

Alfa AF: 0.224 Hom.: 4237

Bravo AF: 0.169

Asia WGS AF: 0.108 AC: 376 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.57

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: rs2006999; hg19: chr6-94082008;