Genetic Variant EGFR:c.*2784A>G (chr7-55208401-A-G) – 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.*2784A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,070 control chromosomes in the GnomAD database, including 4,155 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 0.23 ( 4154 hom., cov: 32)

Exomes 𝑓: 0.18 ( 1 hom. )

Consequence

EGFR
NM_005228.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.*2784A>G		3_prime_UTR_variant	Exon 28 of 28	ENST00000275493.7	NP_005219.2	P00533-1Q504U8F2YGG7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EGFR	ENST00000275493.7 link	c.*2784A>G	3_prime_UTR_variant	Exon 28 of 28	1	NM_005228.5	ENSP00000275493.2	P00533-1
EGFR	ENST00000450046.2 link	c.*2784A>G	3_prime_UTR_variant	Exon 28 of 28	4		ENSP00000413354.2	C9JYS6
EGFR-AS1	ENST00000836806.1 link	n.207+4362T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34415

AN:

151904

Hom.:

4151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.194

GnomAD4 exome

AF:

0.180

AC:

AN:

Hom.:

Cov.:

AF XY:

0.194

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.227

AC:

34443

AN:

152020

Hom.:

4154

Cov.:

AF XY:

0.233

AC XY:

17298

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.315

AC:

13069

AN:

41436

American (AMR)

AF:

0.193

AC:

2944

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

428

AN:

3468

East Asian (EAS)

AF:

0.283

AC:

1457

AN:

5146

South Asian (SAS)

AF:

0.311

AC:

1496

AN:

4814

European-Finnish (FIN)

AF:

0.253

AC:

2675

AN:

10560

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11710

AN:

67986

Other (OTH)

AF:

0.194

AC:

409

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1329

2657

3986

5314

6643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.171

Hom.:

1291

Bravo

AF:

0.222

Asia WGS

AF:

0.316

AC:

1095

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.6

(source)

DANN

Benign

0.22

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

Other links and lift over