7-55201223-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.2982C>T(p.Asp994Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,614,064 control chromosomes in the GnomAD database, including 13,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1060 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12175 hom. )

Consequence

EGFR
NM_005228.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.403

Publications

95 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 links:

EGFR-AS1 (HGNC:40207): (EGFR antisense RNA 1)

EGFR-AS1 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=-0.37).

BP6

Variant 7-55201223-C-T is Benign according to our data. Variant chr7-55201223-C-T is described in ClinVar as Benign. ClinVar VariationId is 259679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.403 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.2982C>T	p.Asp994Asp	synonymous_variant	Exon 25 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.2982C>T	p.Asp994Asp	synonymous_variant	Exon 25 of 28	1	NM_005228.5	ENSP00000275493.2		P00533-1

Frequencies

GnomAD3 genomes

AF:

0.0997

AC:

15164

AN:

152072

Hom.:

1057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0936

GnomAD2 exomes

AF:

0.137

AC:

34569

AN:

251492

AF XY:

0.141

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.0731

Gnomad EAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.0996

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.118

AC:

172092

AN:

1461874

Hom.:

12175

Cov.:

AF XY:

0.120

AC XY:

87503

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0212

AC:

711

AN:

33480

American (AMR)

AF:

0.149

AC:

6660

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0742

AC:

1939

AN:

26136

East Asian (EAS)

AF:

0.310

AC:

12322

AN:

39700

South Asian (SAS)

AF:

0.224

AC:

19326

AN:

86256

European-Finnish (FIN)

AF:

0.193

AC:

10291

AN:

53416

Middle Eastern (MID)

AF:

0.0733

AC:

423

AN:

5768

European-Non Finnish (NFE)

AF:

0.102

AC:

113251

AN:

1111998

Other (OTH)

AF:

0.119

AC:

7169

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9488

18976

28464

37952

47440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4426

8852

13278

17704

22130

<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:

0.0997

AC:

15168

AN:

152190

Hom.:

1060

Cov.:

AF XY:

0.109

AC XY:

8124

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0272

AC:

1129

AN:

41552

American (AMR)

AF:

0.135

AC:

2059

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0726

AC:

252

AN:

3472

East Asian (EAS)

AF:

0.281

AC:

1449

AN:

5152

South Asian (SAS)

AF:

0.234

AC:

1126

AN:

4806

European-Finnish (FIN)

AF:

0.193

AC:

2042

AN:

10602

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6800

AN:

68002

Other (OTH)

AF:

0.0940

AC:

198

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

669

1337

2006

2674

3343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.0985

Hom.:

2941

Bravo

AF:

0.0910

Asia WGS

AF:

0.266

AC:

921

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

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. -

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

-0.37

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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