chr6-93255866-C-T

Variant names:

• chr6-93255866-C-T
• NM_004440.4:c.2344G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004440.4(EPHA7):​c.2344G>A​(p.Val782Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EPHA7 NM_004440.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2720058).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004440.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA7	NM_004440.4	MANE Select	c.2344G>A	p.Val782Ile	missense	Exon 13 of 17	NP_004431.1	Q15375-1
	EPHA7	NM_001376465.1		c.2332G>A	p.Val778Ile	missense	Exon 13 of 17	NP_001363394.1	Q15375-4
	EPHA7	NM_001288629.2		c.2329G>A	p.Val777Ile	missense	Exon 13 of 17	NP_001275558.1	Q15375-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA7	ENST00000369303.9	TSL:1 MANE Select	c.2344G>A	p.Val782Ile	missense	Exon 13 of 17	ENSP00000358309.4	Q15375-1
	EPHA7	ENST00000922908.1		c.2338G>A	p.Val780Ile	missense	Exon 13 of 17	ENSP00000592967.1
	EPHA7	ENST00000680224.1		c.2332G>A	p.Val778Ile	missense	Exon 13 of 17	ENSP00000506130.1	Q15375-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.040
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.35	N
PhyloP100		5.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.26
Sift	Benign	0.13	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.31
MutPred		0.43		Gain of sheet (P = 0.1208)
MVP		0.43
MPC		0.31
ClinPred		0.71	D
GERP RS		5.8
Varity_R		0.057
gMVP		0.67
Mutation Taster		=68/32	polymorphism

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

hg19: chr6-93965584;