rs164547

Positions:

• chr6-93361600-T-A
• chr6-93361600-T-C

Variant summary

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

The NM_004440.4(EPHA7):​c.833-3189A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,852 control chromosomes in the GnomAD database, including 29,607 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 0.62 (29607 hom., cov: 32)
• Consequence: EPHA7 NM_004440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA7	NM_004440.4	c.833-3189A>T		intron_variant		ENST00000369303.9	NP_004431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA7	ENST00000369303.9	c.833-3189A>T		intron_variant		1	NM_004440.4	ENSP00000358309	P3

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94660 AN: 151734 Hom.: 29571 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.624 AC: 94740 AN: 151852 Hom.: 29607 Cov.: 32 AF XY: 0.624 AC XY: 46312 AN XY: 74190

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.609

Alfa AF: 0.599 Hom.: 3399

Bravo AF: 0.631

Asia WGS AF: 0.599 AC: 2084 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.050
DANN	Benign	0.47

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: rs164547; hg19: chr6-94071318;