chr6-93269608-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004440.4(EPHA7):c.1502C>T(p.Ser501Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,599,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
EPHA7
NM_004440.4 missense
NM_004440.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 7.63
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 -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.34205905).
BS2
High AC in GnomAdExome4 at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPHA7 | NM_004440.4 | c.1502C>T | p.Ser501Phe | missense_variant | 7/17 | ENST00000369303.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHA7 | ENST00000369303.9 | c.1502C>T | p.Ser501Phe | missense_variant | 7/17 | 1 | NM_004440.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151616Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000210 AC: 5AN: 238014Hom.: 0 AF XY: 0.0000232 AC XY: 3AN XY: 129292
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GnomAD4 exome AF: 0.0000173 AC: 25AN: 1447510Hom.: 0 Cov.: 30 AF XY: 0.0000236 AC XY: 17AN XY: 720366
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151616Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74010
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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 | Jul 12, 2023 | The c.1502C>T (p.S501F) alteration is located in exon 7 (coding exon 7) of the EPHA7 gene. This alteration results from a C to T substitution at nucleotide position 1502, causing the serine (S) at amino acid position 501 to be replaced by a phenylalanine (F). 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
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of disorder (P = 0.001);
MVP
MPC
ClinPred
D
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