7-55020559-TACACACACACACAC-TACACACACACACACACACAC

Variant names:

• chr7-55020559-T-TACACAC
• rs11568315
• NM_005228.5:c.88+1223_88+1228dupACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005228.5(EGFR):​c.88+1223_88+1228dupACACAC 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
• Publications: 15 publications found

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]

EGFR Gene-Disease associations (from GenCC):

• lung cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
• non-small cell lung carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• inflammatory skin and bowel disease, neonatal, 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neonatal inflammatory skin and bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+1223_88+1228dupACACAC		intron_variant	Intron 1 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.88+1194_88+1195insACACAC		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

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

African (AFR) AF: 0.0966 AC: 3786 AN: 39188

American (AMR) AF: 0.0565 AC: 830 AN: 14688

Ashkenazi Jewish (ASJ) AF: 0.00654 AC: 22 AN: 3366

East Asian (EAS) AF: 0.0547 AC: 266 AN: 4864

South Asian (SAS) AF: 0.0184 AC: 82 AN: 4458

European-Finnish (FIN) AF: 0.0149 AC: 140 AN: 9412

Middle Eastern (MID) AF: 0.0426 AC: 12 AN: 282

European-Non Finnish (NFE) AF: 0.0206 AC: 1355 AN: 65920

Other (OTH) AF: 0.0385 AC: 78 AN: 2026

Alfa AF: 0.00811 Hom.: 145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11568315; hg19: chr7-55088252; COSMIC: COSV51861814;