6-93264637-T-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004440.4(EPHA7):āc.1699A>Gā(p.Ile567Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,607,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000015 ( 0 hom. )
Consequence
EPHA7
NM_004440.4 missense
NM_004440.4 missense
Scores
1
1
17
Clinical Significance
Conservation
PhyloP100: 6.27
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.070314854).
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPHA7 | NM_004440.4 | c.1699A>G | p.Ile567Val | missense_variant | 8/17 | ENST00000369303.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHA7 | ENST00000369303.9 | c.1699A>G | p.Ile567Val | missense_variant | 8/17 | 1 | NM_004440.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151582Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000403 AC: 10AN: 248174Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134224
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1456210Hom.: 0 Cov.: 29 AF XY: 0.00000966 AC XY: 7AN XY: 724484
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151582Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74030
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | The c.1699A>G (p.I567V) alteration is located in exon 8 (coding exon 8) of the EPHA7 gene. This alteration results from a A to G substitution at nucleotide position 1699, causing the isoleucine (I) at amino acid position 567 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of sheet (P = 0.0827);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at