rs7801956

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005228.5(EGFR):c.559+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 1,613,864 control chromosomes in the GnomAD database, including 6,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 418 hom., cov: 33)

Exomes 𝑓: 0.089 ( 6200 hom. )

Consequence

EGFR
NM_005228.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.81

Publications

22 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

EGFR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 7-55146750-G-A is Benign according to our data. Variant chr7-55146750-G-A is described in ClinVar as Benign. ClinVar VariationId is 259681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.559+10G>A		intron_variant	Intron 4 of 27	ENST00000275493.7	NP_005219.2	P00533-1Q504U8F2YGG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 link	c.559+10G>A		intron_variant	Intron 4 of 27	1	NM_005228.5	ENSP00000275493.2		P00533-1

Frequencies

GnomAD3 genomes

AF:

0.0646

AC:

9829

AN:

152118

Hom.:

414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0594

Gnomad ASJ

AF:

0.0974

Gnomad EAS

AF:

0.0553

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.0510

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0911

Gnomad OTH

AF:

0.0769

GnomAD2 exomes

AF:

0.0762

AC:

19130

AN:

251086

AF XY:

0.0805

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.0412

Gnomad ASJ exome

AF:

0.0950

Gnomad EAS exome

AF:

0.0668

Gnomad FIN exome

AF:

0.0492

Gnomad NFE exome

AF:

0.0917

Gnomad OTH exome

AF:

0.0837

GnomAD4 exome

AF:

0.0888

AC:

129804

AN:

1461628

Hom.:

6200

Cov.:

AF XY:

0.0896

AC XY:

65123

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.0163

AC:

545

AN:

33470

American (AMR)

AF:

0.0436

AC:

1948

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0976

AC:

2551

AN:

26130

East Asian (EAS)

AF:

0.0494

AC:

1961

AN:

39692

South Asian (SAS)

AF:

0.106

AC:

9151

AN:

86238

European-Finnish (FIN)

AF:

0.0528

AC:

2816

AN:

53374

Middle Eastern (MID)

AF:

0.0704

AC:

406

AN:

5766

European-Non Finnish (NFE)

AF:

0.0948

AC:

105423

AN:

1111864

Other (OTH)

AF:

0.0829

AC:

5003

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

7064

14127

21191

28254

35318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3926

7852

11778

15704

19630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0647

AC:

9843

AN:

152236

Hom.:

418

Cov.:

AF XY:

0.0636

AC XY:

4737

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0205

AC:

853

AN:

41558

American (AMR)

AF:

0.0593

AC:

908

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0974

AC:

338

AN:

3472

East Asian (EAS)

AF:

0.0552

AC:

286

AN:

5182

South Asian (SAS)

AF:

0.100

AC:

482

AN:

4806

European-Finnish (FIN)

AF:

0.0510

AC:

540

AN:

10596

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0911

AC:

6197

AN:

67992

Other (OTH)

AF:

0.0832

AC:

176

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

467

934

1401

1868

2335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0852

Hom.:

675

Bravo

AF:

0.0632

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 07, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

EGFR-related lung cancer

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lung cancer

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.12

(source)

DANN

Benign

0.41

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over