rs4707795

Variant names:

• chr6-93345150-G-A
• rs4707795
• NM_004440.4:c.1324+11567C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004440.4(EPHA7):​c.1324+11567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,584 control chromosomes in the GnomAD database, including 2,741 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 (2741 hom., cov: 32)
• Consequence: EPHA7 NM_004440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA7	NM_004440.4	c.1324+11567C>T		intron_variant	Intron 5 of 16	ENST00000369303.9	NP_004431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA7	ENST00000369303.9	c.1324+11567C>T		intron_variant	Intron 5 of 16	1	NM_004440.4	ENSP00000358309.4

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26876 AN: 151466 Hom.: 2734 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.177 AC: 26889 AN: 151584 Hom.: 2741 Cov.: 32 AF XY: 0.188 AC XY: 13891 AN XY: 74078

African (AFR) AF: 0.129 AC: 5336 AN: 41444

American (AMR) AF: 0.223 AC: 3375 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3462

East Asian (EAS) AF: 0.355 AC: 1828 AN: 5154

South Asian (SAS) AF: 0.250 AC: 1206 AN: 4824

European-Finnish (FIN) AF: 0.296 AC: 3134 AN: 10582

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11079 AN: 67666

Other (OTH) AF: 0.158 AC: 333 AN: 2104

Alfa AF: 0.169 Hom.: 4176

Bravo AF: 0.169

Asia WGS AF: 0.276 AC: 958 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.41
PhyloP100		0.022
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4707795; hg19: chr6-94054868;