7-55020559-TACACACACACACAC-TACACACACACAC

Variant names:

• chr7-55020559-TAC-T
• rs11568315
• NM_005228.5:c.88+1227_88+1228delAC

Variant summary

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

The NM_005228.5(EGFR):​c.88+1227_88+1228delAC 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 0.027 (104 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 (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+1227_88+1228delAC		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+1195_88+1196delAC		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 3973 AN: 144830 Hom.: 103 Cov.: 0

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.0295

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0263

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0295

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

GnomAD4 genome AF: 0.0275 AC: 3984 AN: 144920 Hom.: 104 Cov.: 0 AF XY: 0.0294 AC XY: 2065 AN XY: 70238

African (AFR) AF: 0.0312 AC: 1224 AN: 39194

American (AMR) AF: 0.0255 AC: 374 AN: 14694

Ashkenazi Jewish (ASJ) AF: 0.0295 AC: 99 AN: 3358

East Asian (EAS) AF: 0.0810 AC: 394 AN: 4862

South Asian (SAS) AF: 0.145 AC: 646 AN: 4448

European-Finnish (FIN) AF: 0.00235 AC: 22 AN: 9370

Middle Eastern (MID) AF: 0.0284 AC: 8 AN: 282

European-Non Finnish (NFE) AF: 0.0175 AC: 1150 AN: 65816

Other (OTH) AF: 0.0332 AC: 67 AN: 2020

Alfa AF: 0.00 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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: COSV51772655;