chr6-93273336-T-C

Position:

• chr6-93273336-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004440.4(EPHA7):​c.1325-914A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,722 control chromosomes in the GnomAD database, including 15,999 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 0.45 (15999 hom., cov: 32)
• Consequence: EPHA7 NM_004440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA7	NM_004440.4	c.1325-914A>G		intron_variant		ENST00000369303.9	NP_004431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA7	ENST00000369303.9	c.1325-914A>G		intron_variant		1	NM_004440.4	ENSP00000358309.4

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67818 AN: 151602 Hom.: 16005 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.447 AC: 67813 AN: 151722 Hom.: 15999 Cov.: 32 AF XY: 0.454 AC XY: 33698 AN XY: 74158

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.472

Alfa AF: 0.335 Hom.: 947

Bravo AF: 0.437

Asia WGS AF: 0.639 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.72

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: rs1548297; hg19: chr6-93983054;