7-55198247-G-C

Variant names:

• chr7-55198247-G-C
• rs2472520
• NM_005228.5:c.2702-470G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.2702-470G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,000 control chromosomes in the GnomAD database, including 17,981 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 0.47 (17981 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2702-470G>C		intron_variant	Intron 22 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2702-470G>C		intron_variant	Intron 22 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71242 AN: 151882 Hom.: 17971 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.469 AC: 71272 AN: 152000 Hom.: 17981 Cov.: 32 AF XY: 0.466 AC XY: 34600 AN XY: 74292

African (AFR) AF: 0.295 AC: 12234 AN: 41468

American (AMR) AF: 0.554 AC: 8465 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2184 AN: 3472

East Asian (EAS) AF: 0.187 AC: 965 AN: 5174

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4812

European-Finnish (FIN) AF: 0.522 AC: 5514 AN: 10558

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38263 AN: 67934

Other (OTH) AF: 0.512 AC: 1076 AN: 2100

Alfa AF: 0.389 Hom.: 1099

Bravo AF: 0.462

Asia WGS AF: 0.329 AC: 1147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.017
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2472520; hg19: chr7-55265940;