7-55156645-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005228.5(EGFR):c.1119G>A(p.Pro373Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000972 in 1,614,192 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P373P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0029 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 5 hom. )

Consequence

EGFR
NM_005228.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.11

Publications

10 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-55156645-G-A is Benign according to our data. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55156645-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 731522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.11 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0029 (442/152298) while in subpopulation AMR AF = 0.0214 (328/15296). AF 95% confidence interval is 0.0195. There are 9 homozygotes in GnomAd4. There are 293 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.1119G>A	p.Pro373Pro	synonymous_variant	Exon 9 of 28	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.1119G>A	p.Pro373Pro	synonymous_variant	Exon 9 of 28	1	NM_005228.5	ENSP00000275493.2		P00533-1

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

443

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00746

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00188

AC:

474

AN:

251484

AF XY:

0.00165

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00662

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00130

Gnomad FIN exome

AF:

0.00716

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000771

AC:

1127

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000727

AC XY:

529

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.00733

AC:

328

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00526

AC:

209

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00751

AC:

401

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000989

AC:

110

AN:

1112012

Other (OTH)

AF:

0.00108

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

162

242

323

404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00290

AC:

442

AN:

152298

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

293

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41580

American (AMR)

AF:

0.0214

AC:

328

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00212

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00746

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68030

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000432

Hom.:

Bravo

AF:

0.00227

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely 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

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EGFR: BP4, BP7, BS1 -

Hereditary cancer-predisposing syndrome

Benign:2

Feb 24, 2021

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Aug 09, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely 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. -

EGFR-related lung cancer

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.67

CADD

Benign

0.17

(source)

DANN

Benign

0.81

PhyloP100

-4.1

Mutation Taster

=100/0

polymorphism

(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