7-55146655-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005228.5(EGFR):c.474C>T(p.Asn158Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,613,822 control chromosomes in the GnomAD database, including 220,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19503 hom., cov: 32)

Exomes 𝑓: 0.52 ( 201148 hom. )

Consequence

EGFR
NM_005228.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.905

Publications

87 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 -19 ACMG points.

BP4

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

BP6

Variant 7-55146655-C-T is Benign according to our data. Variant chr7-55146655-C-T is described in ClinVar as Benign. ClinVar VariationId is 259680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.905 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.474C>T	p.Asn158Asn	synonymous_variant	Exon 4 of 28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 link	c.474C>T	p.Asn158Asn	synonymous_variant	Exon 4 of 28	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76735

AN:

151856

Hom.:

19469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.498

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.522

Gnomad OTH

AF:

0.503

GnomAD2 exomes

AF:

0.511

AC:

128445

AN:

251406

AF XY:

0.511

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.568

Gnomad EAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.520

Gnomad OTH exome

AF:

0.500

GnomAD4 exome

AF:

0.523

AC:

764184

AN:

1461848

Hom.:

201148

Cov.:

AF XY:

0.523

AC XY:

380414

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.501

AC:

16766

AN:

33480

American (AMR)

AF:

0.524

AC:

23439

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

14804

AN:

26136

East Asian (EAS)

AF:

0.333

AC:

13226

AN:

39698

South Asian (SAS)

AF:

0.551

AC:

47529

AN:

86258

European-Finnish (FIN)

AF:

0.493

AC:

26351

AN:

53408

Middle Eastern (MID)

AF:

0.527

AC:

3038

AN:

5768

European-Non Finnish (NFE)

AF:

0.528

AC:

587624

AN:

1111984

Other (OTH)

AF:

0.520

AC:

31407

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

24665

49330

73996

98661

123326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16818

33636

50454

67272

84090

<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:

0.506

AC:

76824

AN:

151974

Hom.:

19503

Cov.:

AF XY:

0.500

AC XY:

37143

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.499

AC:

20674

AN:

41468

American (AMR)

AF:

0.494

AC:

7535

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

1921

AN:

3466

East Asian (EAS)

AF:

0.351

AC:

1806

AN:

5142

South Asian (SAS)

AF:

0.543

AC:

2615

AN:

4812

European-Finnish (FIN)

AF:

0.482

AC:

5086

AN:

10560

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.522

AC:

35510

AN:

67962

Other (OTH)

AF:

0.507

AC:

1069

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1979

3958

5938

7917

9896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.516

Hom.:

83736

Bravo

AF:

0.506

Asia WGS

AF:

0.463

AC:

1612

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

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

- -

Jan 10, 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

- -

Hereditary cancer-predisposing syndrome

Benign:1

Oct 18, 2024

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jul 30, 2021

Genome-Nilou Lab

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

-0.28

CADD

Benign

9.9

(source)

DANN

Benign

0.69

PhyloP100

0.91

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

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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