7-55020559-TACACACACACACAC-TACACACACACACACACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005228.5(EGFR):c.88+1215_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 0.0023 (6 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00225 (327/145234) while in subpopulation AFR AF= 0.0054 (212/39236). AF 95% confidence interval is 0.00481. There are 6 homozygotes in gnomad4. There are 140 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+1215_88+1228dup		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+1215_88+1228dup		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 327 AN: 145144 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.00542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00185

Gnomad SAS AF: 0.00447

Gnomad FIN AF: 0.000211

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000849

Gnomad OTH AF: 0.00149

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

GnomAD4 genome AF: 0.00225 AC: 327 AN: 145234 Hom.: 6 Cov.: 0 AF XY: 0.00199 AC XY: 140 AN XY: 70410

Gnomad4 AFR AF: 0.00540

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00185

Gnomad4 SAS AF: 0.00448

Gnomad4 FIN AF: 0.000211

Gnomad4 NFE AF: 0.000849

Gnomad4 OTH AF: 0.00148

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;