Genetic Variant EGFR:c.*5542C>A (chr7-55211159-C-A) – 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.*5542C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,044 control chromosomes in the GnomAD database, including 13,175 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 0.38 ( 13174 hom., cov: 33)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

EGFR
NM_005228.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.618

Publications

13 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.*5542C>A		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.*5542C>A	3_prime_UTR_variant	Exon 28 of 28	1	NM_005228.5	ENSP00000275493.2	P00533-1
EGFR	ENST00000450046.2 link	c.*5542C>A	3_prime_UTR_variant	Exon 28 of 28	4		ENSP00000413354.2	C9JYS6
EGFR-AS1	ENST00000836806.1 link	n.207+1604G>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58427

AN:

151922

Hom.:

13142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.584

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.747

Gnomad SAS

AF:

0.508

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.343

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

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:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

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:

0.385

AC:

58508

AN:

152040

Hom.:

13174

Cov.:

AF XY:

0.393

AC XY:

29187

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.584

AC:

24205

AN:

41438

American (AMR)

AF:

0.312

AC:

4763

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

693

AN:

3468

East Asian (EAS)

AF:

0.748

AC:

3862

AN:

5162

South Asian (SAS)

AF:

0.508

AC:

2449

AN:

4822

European-Finnish (FIN)

AF:

0.348

AC:

3676

AN:

10574

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17748

AN:

67978

Other (OTH)

AF:

0.343

AC:

725

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1659

3318

4978

6637

8296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.286

Hom.:

3800

Bravo

AF:

0.391

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.70

(source)

DANN

Benign

0.50

PhyloP100

-0.62

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

Computational scores

Splicing

Publications

Other links and lift over