7-55020559-TACACACACACACAC-TACACACACACACACACACAC

Variant summary

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

The NM_005228.5(EGFR):c.88+1223_88+1228dup 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 0.045 (231 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 (AFR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+1223_88+1228dup		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+1223_88+1228dup		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6550 AN: 144990 Hom.: 230 Cov.: 0

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.00654

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0395

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0364

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

GnomAD4 genome AF: 0.0453 AC: 6571 AN: 145080 Hom.: 231 Cov.: 0 AF XY: 0.0448 AC XY: 3153 AN XY: 70324

Gnomad4 AFR AF: 0.0966

Gnomad4 AMR AF: 0.0565

Gnomad4 ASJ AF: 0.00654

Gnomad4 EAS AF: 0.0547

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;