6-93273336-T-C

Variant names:

• chr6-93273336-T-C
• rs1548297
• NM_004440.4:c.1325-914A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 rank	MANE	Protein	UniProt
EPHA7	NM_004440.4	c.1325-914A>G		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.1325-914A>G		intron_variant	Intron 5 of 16	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

African (AFR) AF: 0.317 AC: 13143 AN: 41420

American (AMR) AF: 0.453 AC: 6895 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1785 AN: 3458

East Asian (EAS) AF: 0.651 AC: 3340 AN: 5130

South Asian (SAS) AF: 0.698 AC: 3358 AN: 4814

European-Finnish (FIN) AF: 0.465 AC: 4902 AN: 10544

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32745 AN: 67828

Other (OTH) AF: 0.472 AC: 993 AN: 2106

Alfa AF: 0.333 Hom.: 986

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
PhyloP100		0.56
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: rs1548297; hg19: chr6-93983054;