rs2302535

Positions:

• chr7-55086995-A-C
• chr7-55086995-A-G
• chr7-55086995-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005228.5(EGFR):​c.89-55291A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,946 control chromosomes in the GnomAD database, including 7,553 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 0.27 (7553 hom., cov: 31)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.89-55291A>C		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.89-55291A>C		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40806 AN: 151828 Hom.: 7548 Cov.: 31

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.269 AC: 40806 AN: 151946 Hom.: 7553 Cov.: 31 AF XY: 0.281 AC XY: 20836 AN XY: 74276

Gnomad4 AFR AF: 0.0806

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.281

Alfa AF: 0.145 Hom.: 315

Bravo AF: 0.270

Asia WGS AF: 0.542 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.87

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

LitVar

Other links and lift over

dbSNP: rs2302535; hg19: chr7-55154688;