chr7-55073624-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005228.5(EGFR):​c.88+54259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,172 control chromosomes in the GnomAD database, including 9,148 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 9148 hom., cov: 33)

Consequence

EGFR
NM_005228.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

Publications

15 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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EGFRNM_005228.5 linkc.88+54259T>C intron_variant Intron 1 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.88+54259T>C intron_variant Intron 1 of 27 1 NM_005228.5 ENSP00000275493.2 P00533-1

Frequencies

GnomAD3 genomes
AF:
0.301
AC:
45764
AN:
152054
Hom.:
9112
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.572
Gnomad AMI
AF:
0.155
Gnomad AMR
AF:
0.269
Gnomad ASJ
AF:
0.170
Gnomad EAS
AF:
0.0911
Gnomad SAS
AF:
0.213
Gnomad FIN
AF:
0.210
Gnomad MID
AF:
0.203
Gnomad NFE
AF:
0.191
Gnomad OTH
AF:
0.251
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.301
AC:
45872
AN:
152172
Hom.:
9148
Cov.:
33
AF XY:
0.298
AC XY:
22188
AN XY:
74396
show subpopulations
African (AFR)
AF:
0.572
AC:
23722
AN:
41470
American (AMR)
AF:
0.270
AC:
4124
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.170
AC:
589
AN:
3472
East Asian (EAS)
AF:
0.0911
AC:
472
AN:
5180
South Asian (SAS)
AF:
0.213
AC:
1029
AN:
4826
European-Finnish (FIN)
AF:
0.210
AC:
2230
AN:
10606
Middle Eastern (MID)
AF:
0.207
AC:
61
AN:
294
European-Non Finnish (NFE)
AF:
0.191
AC:
12959
AN:
68008
Other (OTH)
AF:
0.258
AC:
545
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1463
2926
4388
5851
7314
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
432
864
1296
1728
2160
<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:
0.253
Hom.:
2657
Bravo
AF:
0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
2.9
DANN
Benign
0.41
PhyloP100
0.070
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: rs17172432; hg19: chr7-55141317; API