7-55020559-TACACACACACACAC-TACACACACACACACACACACACAC

Variant names:

• chr7-55020559-T-TACACACACAC
• rs11568315
• NM_005228.5:c.88+1219_88+1228dupACACACACAC

Variant summary

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

The NM_005228.5(EGFR):​c.88+1219_88+1228dupACACACACAC 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
• 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 = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+1219_88+1228dupACACACACAC		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+1195insACACACACAC		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

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

African (AFR) AF: 0.0721 AC: 2826 AN: 39188

American (AMR) AF: 0.0592 AC: 871 AN: 14702

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 215 AN: 3360

East Asian (EAS) AF: 0.0553 AC: 269 AN: 4868

South Asian (SAS) AF: 0.0517 AC: 230 AN: 4452

European-Finnish (FIN) AF: 0.0474 AC: 448 AN: 9450

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

European-Non Finnish (NFE) AF: 0.0596 AC: 3924 AN: 65894

Other (OTH) AF: 0.0562 AC: 114 AN: 2028

Alfa AF: 0.0323 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;