6-93298817-C-T

Variant names:

• chr6-93298817-C-T
• rs9363058
• NM_004440.4:c.1325-26395G>A

Variant summary

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

The NM_004440.4(EPHA7):​c.1325-26395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,992 control chromosomes in the GnomAD database, including 4,947 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 0.24 (4947 hom., cov: 32)
• Consequence: EPHA7 NM_004440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA7	NM_004440.4	c.1325-26395G>A		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.1325-26395G>A		intron_variant	Intron 5 of 16	1	NM_004440.4	ENSP00000358309.4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35977 AN: 151874 Hom.: 4948 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.237 AC: 35971 AN: 151992 Hom.: 4947 Cov.: 32 AF XY: 0.240 AC XY: 17857 AN XY: 74284

African (AFR) AF: 0.101 AC: 4182 AN: 41462

American (AMR) AF: 0.227 AC: 3471 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3470

East Asian (EAS) AF: 0.171 AC: 882 AN: 5162

South Asian (SAS) AF: 0.309 AC: 1489 AN: 4826

European-Finnish (FIN) AF: 0.368 AC: 3878 AN: 10528

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.296 AC: 20103 AN: 67958

Other (OTH) AF: 0.229 AC: 483 AN: 2106

Alfa AF: 0.280 Hom.: 10110

Bravo AF: 0.222

Asia WGS AF: 0.221 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.55
PhyloP100		-0.45
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: rs9363058; hg19: chr6-94008535;