dbSNP rs3735063: EGFR:c.89-56815T>C (chr7-55085471-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005228.5(EGFR):c.89-56815T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,336 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 56 hom., cov: 33)

Consequence

EGFR
NM_005228.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.82

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.89-56815T>C		intron_variant	Intron 1 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.89-56815T>C		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2		P00533-1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2903

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0356

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0395

Gnomad SAS

AF:

0.0673

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00658

Gnomad OTH

AF:

0.0172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0192

AC:

2919

AN:

152336

Hom.:

Cov.:

AF XY:

0.0203

AC XY:

1514

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0356

AC:

1482

AN:

41578

American (AMR)

AF:

0.0107

AC:

164

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3472

East Asian (EAS)

AF:

0.0396

AC:

205

AN:

5176

South Asian (SAS)

AF:

0.0674

AC:

325

AN:

4822

European-Finnish (FIN)

AF:

0.0101

AC:

107

AN:

10622

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00658

AC:

448

AN:

68034

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

141

281

422

562

703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0142

Hom.:

Bravo

AF:

0.0182

Asia WGS

AF:

0.0860

AC:

299

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.15

(source)

DANN

Benign

0.31

PhyloP100

-2.8

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over