rs17290162
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005228.5(EGFR):c.1788G>A(p.Pro596Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,614,122 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0082 ( 19 hom., cov: 33)
Exomes 𝑓: 0.00093 ( 28 hom. )
Consequence
EGFR
NM_005228.5 synonymous
NM_005228.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.72
Genes affected
EGFR (HGNC:3236): (epidermal growth factor receptor) The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor, thus inducing receptor dimerization and tyrosine autophosphorylation leading to cell proliferation. Mutations in this gene are associated with lung cancer. EGFR is a component of the cytokine storm which contributes to a severe form of Coronavirus Disease 2019 (COVID-19) resulting from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 7-55165345-G-A is Benign according to our data. Variant chr7-55165345-G-A is described in ClinVar as [Benign]. Clinvar id is 782268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.72 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00817 (1244/152270) while in subpopulation AFR AF= 0.0281 (1169/41532). AF 95% confidence interval is 0.0268. There are 19 homozygotes in gnomad4. There are 608 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 19 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.1788G>A | p.Pro596Pro | synonymous_variant | 15/28 | ENST00000275493.7 | NP_005219.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.1788G>A | p.Pro596Pro | synonymous_variant | 15/28 | 1 | NM_005228.5 | ENSP00000275493.2 |
Frequencies
GnomAD3 genomes AF: 0.00814 AC: 1239AN: 152154Hom.: 19 Cov.: 33
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GnomAD3 exomes AF: 0.00203 AC: 510AN: 251426Hom.: 7 AF XY: 0.00166 AC XY: 225AN XY: 135892
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GnomAD4 exome AF: 0.000926 AC: 1354AN: 1461852Hom.: 28 Cov.: 31 AF XY: 0.000770 AC XY: 560AN XY: 727228
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GnomAD4 genome AF: 0.00817 AC: 1244AN: 152270Hom.: 19 Cov.: 33 AF XY: 0.00817 AC XY: 608AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | May 12, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
EGFR-related lung cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 09, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at