NM_005228.5:c.2184+100C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005228.5(EGFR):​c.2184+100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,513,934 control chromosomes in the GnomAD database, including 1,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 225 hom., cov: 33)
Exomes 𝑓: 0.041 ( 1302 hom. )

Consequence

EGFR
NM_005228.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.765

Publications

6 publications found
Variant links:
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 cancer
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
  • non-small cell lung carcinoma
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • inflammatory skin and bowel disease, neonatal, 2
    Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • neonatal inflammatory skin and bowel disease
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 7-55174143-C-T is Benign according to our data. Variant chr7-55174143-C-T is described in ClinVar as [Benign]. Clinvar id is 1228216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EGFRNM_005228.5 linkc.2184+100C>T intron_variant Intron 18 of 27 ENST00000275493.7 NP_005219.2 P00533-1Q504U8F2YGG7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EGFRENST00000275493.7 linkc.2184+100C>T intron_variant Intron 18 of 27 1 NM_005228.5 ENSP00000275493.2 P00533-1
EGFRENST00000455089.5 linkc.2049+100C>T intron_variant Intron 17 of 25 1 ENSP00000415559.1 Q504U8
EGFRENST00000450046.2 linkc.2025+100C>T intron_variant Intron 18 of 27 4 ENSP00000413354.2 C9JYS6
EGFRENST00000700145.1 linkc.531+100C>T intron_variant Intron 5 of 8 ENSP00000514824.1 A0A8V8TPW8

Frequencies

GnomAD3 genomes
AF:
0.0509
AC:
7743
AN:
152210
Hom.:
227
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0783
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.0426
Gnomad ASJ
AF:
0.0766
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.0217
Gnomad FIN
AF:
0.0168
Gnomad MID
AF:
0.114
Gnomad NFE
AF:
0.0461
Gnomad OTH
AF:
0.0569
GnomAD4 exome
AF:
0.0413
AC:
56217
AN:
1361606
Hom.:
1302
AF XY:
0.0409
AC XY:
27607
AN XY:
675406
show subpopulations
African (AFR)
AF:
0.0808
AC:
2468
AN:
30560
American (AMR)
AF:
0.0327
AC:
1149
AN:
35118
Ashkenazi Jewish (ASJ)
AF:
0.0678
AC:
1619
AN:
23868
East Asian (EAS)
AF:
0.0000786
AC:
3
AN:
38190
South Asian (SAS)
AF:
0.0233
AC:
1827
AN:
78304
European-Finnish (FIN)
AF:
0.0192
AC:
916
AN:
47790
Middle Eastern (MID)
AF:
0.0689
AC:
308
AN:
4470
European-Non Finnish (NFE)
AF:
0.0432
AC:
45257
AN:
1046872
Other (OTH)
AF:
0.0473
AC:
2670
AN:
56434
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
2605
5209
7814
10418
13023
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1666
3332
4998
6664
8330
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0508
AC:
7745
AN:
152328
Hom.:
225
Cov.:
33
AF XY:
0.0491
AC XY:
3656
AN XY:
74494
show subpopulations
African (AFR)
AF:
0.0782
AC:
3250
AN:
41568
American (AMR)
AF:
0.0425
AC:
651
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.0766
AC:
266
AN:
3472
East Asian (EAS)
AF:
0.000386
AC:
2
AN:
5186
South Asian (SAS)
AF:
0.0220
AC:
106
AN:
4828
European-Finnish (FIN)
AF:
0.0168
AC:
178
AN:
10620
Middle Eastern (MID)
AF:
0.112
AC:
33
AN:
294
European-Non Finnish (NFE)
AF:
0.0461
AC:
3136
AN:
68026
Other (OTH)
AF:
0.0568
AC:
120
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
385
771
1156
1542
1927
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
86
172
258
344
430
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0532
Hom.:
34
Bravo
AF:
0.0549
Asia WGS
AF:
0.0180
AC:
64
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Mar 16, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.8
DANN
Benign
0.43
PhyloP100
-0.77
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs17290336; hg19: chr7-55241836; COSMIC: COSV51776814; API