rs17337135
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005228.5(EGFR):c.2283+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,243,416 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.019 ( 33 hom., cov: 33)
Exomes 𝑓: 0.023 ( 356 hom. )
Consequence
EGFR
NM_005228.5 intron
NM_005228.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.724
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 7-55174889-G-A is Benign according to our data. Variant chr7-55174889-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1191430.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2931/152286) while in subpopulation NFE AF= 0.0276 (1880/68030). AF 95% confidence interval is 0.0266. There are 33 homozygotes in gnomad4. There are 1311 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGFR | NM_005228.5 | c.2283+69G>A | intron_variant | ENST00000275493.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGFR | ENST00000275493.7 | c.2283+69G>A | intron_variant | 1 | NM_005228.5 | P1 | |||
EGFR | ENST00000455089.5 | c.2148+69G>A | intron_variant | 1 | |||||
EGFR | ENST00000450046.2 | c.2124+69G>A | intron_variant | 4 | |||||
EGFR | ENST00000700145.1 | c.632+69G>A | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0193 AC: 2935AN: 152168Hom.: 33 Cov.: 33
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GnomAD4 exome AF: 0.0227 AC: 24725AN: 1091130Hom.: 356 AF XY: 0.0227 AC XY: 12685AN XY: 559150
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GnomAD4 genome ? AF: 0.0192 AC: 2931AN: 152286Hom.: 33 Cov.: 33 AF XY: 0.0176 AC XY: 1311AN XY: 74450
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 16, 2019 | - - |
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