rs2280653

Variant names:

• chr7-55208401-A-G
• rs2280653
• NM_005228.5:c.*2784A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-55208401-A-G
• chr7-55208401-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

ACMG classification

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	c.*2784A>G		3_prime_UTR_variant	Exon 28 of 28	ENST00000275493.7	NP_005219.2

Ensembl

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

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 5 AN: 40

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

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: 41 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11710 AN: 67986

Other (OTH) AF: 0.194 AC: 409 AN: 2112

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
DANN	Benign	0.22
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2280653; hg19: chr7-55276094;