rs2280653

chr7-55208401-A-Gchr7-55208401-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EGFR	NM_005228.5	c.*2784A>G		3_prime_UTR_variant	28/28	ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.*2784A>G		3_prime_UTR_variant	28/28	1	NM_005228.5	P1
EGFR	ENST00000450046.2	c.*2784A>G		3_prime_UTR_variant	28/28	4

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34415 AN: 151904 Hom.: 4151 Cov.: 32

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: 9 AN: 50 Hom.: 1 Cov.: 0 AF XY: 0.194 AC XY: 7 AN XY: 36

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.227 AC: 34443 AN: 152020 Hom.: 4154 Cov.: 32 AF XY: 0.233 AC XY: 17298 AN XY: 74300

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.194

Alfa AF: 0.133 Hom.: 350

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
Dann	Benign	0.22

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

LitVar

Other links and lift over

dbSNP: rs2280653; hg19: chr7-55276094;