7-55020559-TACACACACACACAC-TACACACACACACACACACACACACAC

Variant summary

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

The NM_005228.5(EGFR):c.88+1217_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 0.0095 (14 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 sas. gnomad4 allele frequency = 0.00948 (1376/145206) while in subpopulation SAS AF= 0.0305 (136/4456). AF 95% confidence interval is 0.0263. There are 14 homozygotes in gnomad4. There are 708 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+1217_88+1228dup		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+1217_88+1228dup		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.00950 AC: 1378 AN: 145116 Hom.: 14 Cov.: 0

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.0143

Gnomad EAS AF: 0.0178

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00987

Gnomad NFE AF: 0.00409

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.00948 AC: 1376 AN: 145206 Hom.: 14 Cov.: 0 AF XY: 0.0101 AC XY: 708 AN XY: 70394

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.00686

Gnomad4 ASJ AF: 0.0143

Gnomad4 EAS AF: 0.0179

Gnomad4 SAS AF: 0.0305

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.00409

Gnomad4 OTH AF: 0.0108

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;