7-55020559-TACACACACACACAC-TACACACACACAC

Position:

• chr7-55020559-TACACACACACACAC-TACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005228.5(EGFR):​c.88+1227_88+1228del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.027 (104 hom., cov: 0)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+1227_88+1228del		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.88+1227_88+1228del		intron_variant		1	NM_005228.5	ENSP00000275493	P1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 3973 AN: 144830 Hom.: 103 Cov.: 0

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.0295

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0263

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0295

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

GnomAD4 genome AF: 0.0275 AC: 3984 AN: 144920 Hom.: 104 Cov.: 0 AF XY: 0.0294 AC XY: 2065 AN XY: 70238

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0295

Gnomad4 EAS AF: 0.0810

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs11568315; hg19: chr7-55088252;