rs1050171

Positions:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_005228.5(EGFR):c.2361G>A(p.Gln787Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.558 in 1,613,948 control chromosomes in the GnomAD database, including 257,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 21009 hom., cov: 33)

Exomes 𝑓: 0.56 ( 236892 hom. )

Consequence

EGFR
NM_005228.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 4.23

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:

EGFR-AS1 (HGNC:):

EGFR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 7-55181370-G-A is Benign according to our data. Variant chr7-55181370-G-A is described in ClinVar as [Benign]. Clinvar id is 45271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55181370-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 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.2361G>A	p.Gln787Gln	synonymous_variant	20/28	ENST00000275493.7	NP_005219.2	P00533-1Q504U8F2YGG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 linkuse as main transcript	c.2361G>A	p.Gln787Gln	synonymous_variant	20/28	1	NM_005228.5	ENSP00000275493.2		P00533-1

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78151

AN:

151962

Hom.:

20991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.548

GnomAD3 exomes

AF:

0.524

AC:

131687

AN:

251430

Hom.:

36653

AF XY:

0.530

AC XY:

72070

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.409

Gnomad AMR exome

AF:

0.549

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.172

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.466

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.585

GnomAD4 exome

AF:

0.563

AC:

822502

AN:

1461868

Hom.:

236892

Cov.:

AF XY:

0.563

AC XY:

409475

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.400

Gnomad4 AMR exome

AF:

0.557

Gnomad4 ASJ exome

AF:

0.667

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.508

Gnomad4 FIN exome

AF:

0.470

Gnomad4 NFE exome

AF:

0.589

Gnomad4 OTH exome

AF:

0.550

GnomAD4 genome

AF:

0.514

AC:

78200

AN:

152080

Hom.:

21009

Cov.:

AF XY:

0.505

AC XY:

37542

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.554

Gnomad4 ASJ

AF:

0.661

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.480

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.594

Gnomad4 OTH

AF:

0.550

Alfa

AF:

0.567

Hom.:

17587

Bravo

AF:

0.517

Asia WGS

AF:

0.371

AC:

1291

AN:

3478

EpiCase

AF:

0.618

EpiControl

AF:

0.604

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 05, 2017	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	This variant is associated with the following publications: (PMID: 17409930, 17956637) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Lung carcinoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Squamous cell lung carcinoma

Benign:1

Likely benign, no assertion criteria provided

clinical testing;in vivo

Faculté Pluridciplinaire Nador, Université Mohamed Premier

May 05, 2020

- -

EGFR-related lung cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Lung cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Inflammatory skin and bowel disease, neonatal, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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