rs2227984
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005228.5(EGFR):c.1887T>A(p.Thr629=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,613,896 control chromosomes in the GnomAD database, including 103,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.34 ( 9180 hom., cov: 33)
Exomes 𝑓: 0.35 ( 93898 hom. )
Consequence
EGFR
NM_005228.5 synonymous
NM_005228.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.663
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=-0.82).
BP6
Variant 7-55171181-T-A is Benign according to our data. Variant chr7-55171181-T-A is described in ClinVar as [Benign]. Clinvar id is 259677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55171181-T-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.663 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.1887T>A | p.Thr629= | synonymous_variant | 16/28 | ENST00000275493.7 | NP_005219.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.1887T>A | p.Thr629= | synonymous_variant | 16/28 | 1 | NM_005228.5 | ENSP00000275493 | P1 | |
EGFR | ENST00000455089.5 | c.1752T>A | p.Thr584= | synonymous_variant | 15/26 | 1 | ENSP00000415559 | |||
EGFR | ENST00000450046.2 | c.1728T>A | p.Thr576= | synonymous_variant | 16/28 | 4 | ENSP00000413354 | |||
EGFR | ENST00000700145.1 | c.237T>A | p.Thr79= | synonymous_variant | 3/9 | ENSP00000514824 |
Frequencies
GnomAD3 genomes AF: 0.341 AC: 51789AN: 152040Hom.: 9181 Cov.: 33
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GnomAD3 exomes AF: 0.376 AC: 94569AN: 251376Hom.: 18426 AF XY: 0.380 AC XY: 51581AN XY: 135860
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GnomAD4 exome AF: 0.353 AC: 516104AN: 1461738Hom.: 93898 Cov.: 44 AF XY: 0.356 AC XY: 258718AN XY: 727188
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GnomAD4 genome AF: 0.340 AC: 51801AN: 152158Hom.: 9180 Cov.: 33 AF XY: 0.345 AC XY: 25637AN XY: 74380
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 07, 2019 | - - |
EGFR-related lung cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Lung cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Inflammatory skin and bowel disease, neonatal, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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