7-55020559-TACACACACACACAC-TACACACACACACACACACACACAC

Variant summary

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

The NM_005228.5(EGFR):c.88+1219_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 0.061 (281 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 = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+1219_88+1228dup		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+1219_88+1228dup		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 8910 AN: 145010 Hom.: 278 Cov.: 0

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.0137

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.0461

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0563

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

GnomAD4 genome AF: 0.0615 AC: 8921 AN: 145100 Hom.: 281 Cov.: 0 AF XY: 0.0602 AC XY: 4236 AN XY: 70336

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.0553

Gnomad4 SAS AF: 0.0517

Gnomad4 FIN AF: 0.0474

Gnomad4 NFE AF: 0.0596

Gnomad4 OTH AF: 0.0562

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;