rs712830

chr7-55019087-A-Cchr7-55019087-A-Gchr7-55019087-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.869

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]

ACMG classification

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
EGFR	NM_005228.5	c.-191A>C		5_prime_UTR_variant	1/28	ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.-191A>C		5_prime_UTR_variant	1/28	1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.892 AC: 134487 AN: 150764 Hom.: 60232 Cov.: 33

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

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

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Lung cancer Benign:1

Likely benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 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

Other links and lift over

dbSNP: rs712830; hg19: chr7-55086780;