rs771210838
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_005228.5(EGFR):c.11C>A(p.Ser4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,354,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S4F) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Consequence
EGFR
NM_005228.5 missense
NM_005228.5 missense
Scores
2
2
14
Clinical Significance
Conservation
PhyloP100: -0.142
Publications
29 publications found
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]
EGFR Gene-Disease associations (from GenCC):
- lung cancerInheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
- non-small cell lung carcinomaInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- inflammatory skin and bowel disease, neonatal, 2Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- neonatal inflammatory skin and bowel diseaseInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27177566).
BP6
Variant 7-55019288-C-A is Benign according to our data. Variant chr7-55019288-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 957645.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005228.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EGFR | TSL:1 MANE Select | c.11C>A | p.Ser4Tyr | missense | Exon 1 of 28 | ENSP00000275493.2 | P00533-1 | ||
| EGFR | TSL:1 | c.11C>A | p.Ser4Tyr | missense | Exon 1 of 26 | ENSP00000415559.1 | Q504U8 | ||
| EGFR | TSL:1 | c.11C>A | p.Ser4Tyr | missense | Exon 1 of 16 | ENSP00000345973.2 | P00533-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000636 AC: 1AN: 157216 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
157216
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000148 AC: 2AN: 1354588Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 671606 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1354588
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
671606
show subpopulations
African (AFR)
AF:
AC:
0
AN:
27868
American (AMR)
AF:
AC:
1
AN:
35626
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
22846
East Asian (EAS)
AF:
AC:
0
AN:
30276
South Asian (SAS)
AF:
AC:
0
AN:
77546
European-Finnish (FIN)
AF:
AC:
0
AN:
46290
Middle Eastern (MID)
AF:
AC:
0
AN:
5022
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1054572
Other (OTH)
AF:
AC:
0
AN:
54542
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
1
-
EGFR-related lung cancer (1)
-
-
1
Hereditary cancer-predisposing syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of disorder (P = 0.001)
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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