7-55019087-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005228.5(EGFR):​c.-191A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 305,792 control chromosomes in the GnomAD database, including 117,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60271 hom., cov: 33)
Exomes 𝑓: 0.86 ( 57599 hom. )

Consequence

EGFR
NM_005228.5 5_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.869
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 7-55019087-A-C is Benign according to our data. Variant chr7-55019087-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1232163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EGFRNM_005228.5 linkuse as main transcriptc.-191A>C 5_prime_UTR_variant 1/28 ENST00000275493.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EGFRENST00000275493.7 linkuse as main transcriptc.-191A>C 5_prime_UTR_variant 1/281 NM_005228.5 P1P00533-1

Frequencies

GnomAD3 genomes
AF:
0.892
AC:
134487
AN:
150764
Hom.:
60232
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.973
Gnomad AMI
AF:
0.950
Gnomad AMR
AF:
0.825
Gnomad ASJ
AF:
0.903
Gnomad EAS
AF:
0.998
Gnomad SAS
AF:
0.952
Gnomad FIN
AF:
0.824
Gnomad MID
AF:
0.943
Gnomad NFE
AF:
0.854
Gnomad OTH
AF:
0.907
GnomAD4 exome
AF:
0.860
AC:
133275
AN:
154922
Hom.:
57599
Cov.:
3
AF XY:
0.860
AC XY:
69860
AN XY:
81212
show subpopulations
Gnomad4 AFR exome
AF:
0.968
Gnomad4 AMR exome
AF:
0.794
Gnomad4 ASJ exome
AF:
0.899
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
0.938
Gnomad4 FIN exome
AF:
0.806
Gnomad4 NFE exome
AF:
0.843
Gnomad4 OTH exome
AF:
0.872
GnomAD4 genome
AF:
0.892
AC:
134576
AN:
150870
Hom.:
60271
Cov.:
33
AF XY:
0.890
AC XY:
65571
AN XY:
73662
show subpopulations
Gnomad4 AFR
AF:
0.973
Gnomad4 AMR
AF:
0.825
Gnomad4 ASJ
AF:
0.903
Gnomad4 EAS
AF:
0.998
Gnomad4 SAS
AF:
0.952
Gnomad4 FIN
AF:
0.824
Gnomad4 NFE
AF:
0.854
Gnomad4 OTH
AF:
0.905
Alfa
AF:
0.874
Hom.:
7232
Bravo
AF:
0.895
Asia WGS
AF:
0.949
AC:
3123
AN:
3292

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJan 10, 2019- -
Lung cancer Benign:1
Likely benign, criteria provided, single submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
8.7
DANN
Benign
0.38

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs712830; hg19: chr7-55086780; API