chr7-55146694-C-T
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_005228.5(EGFR):c.513C>T(p.Asp171=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,614,194 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
EGFR
NM_005228.5 synonymous
NM_005228.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.75
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 -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 7-55146694-C-T is Benign according to our data. Variant chr7-55146694-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1167861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.75 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000341 (52/152306) while in subpopulation AFR AF= 0.00123 (51/41568). AF 95% confidence interval is 0.000958. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.513C>T | p.Asp171= | synonymous_variant | 4/28 | ENST00000275493.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.513C>T | p.Asp171= | synonymous_variant | 4/28 | 1 | NM_005228.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000123 AC: 31AN: 251452Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135908
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GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461888Hom.: 0 Cov.: 36 AF XY: 0.0000289 AC XY: 21AN XY: 727246
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GnomAD4 genome AF: 0.000341 AC: 52AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20AN XY: 74474
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
EGFR-related lung cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 06, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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