Variant 7-55019087-A-C details in Genebe, Genetics Data Aggregator

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

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]

EGFR links:

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	Protein	UniProt
EGFR	NM_005228.5 linkuse as main transcript	c.-191A>C		5_prime_UTR_variant	1/28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 linkuse as main transcript	c.-191A>C		5_prime_UTR_variant	1/28	1	NM_005228.5	ENSP00000275493	P1	P00533-1

Frequencies

GnomAD3 genomes

AF:

0.892

AC:

134487

AN:

150764

Hom.:

60232

Cov.:

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.:

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.:

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over