NM_005228.5:c.88+1227_88+1228dupAC

Variant names:

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

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+1228dupAC 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 0.087 (674 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 = 0.156 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+1228dupAC		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+1195insAC		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 12531 AN: 144966 Hom.: 671 Cov.: 0

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0240

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.0776

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.112

Gnomad NFE AF: 0.0558

Gnomad OTH AF: 0.0857

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

GnomAD4 genome AF: 0.0865 AC: 12551 AN: 145054 Hom.: 674 Cov.: 0 AF XY: 0.0867 AC XY: 6097 AN XY: 70324

African (AFR) AF: 0.159 AC: 6242 AN: 39178

American (AMR) AF: 0.0607 AC: 892 AN: 14684

Ashkenazi Jewish (ASJ) AF: 0.0776 AC: 261 AN: 3364

East Asian (EAS) AF: 0.0313 AC: 152 AN: 4862

South Asian (SAS) AF: 0.0632 AC: 282 AN: 4460

European-Finnish (FIN) AF: 0.0867 AC: 817 AN: 9418

Middle Eastern (MID) AF: 0.113 AC: 32 AN: 282

European-Non Finnish (NFE) AF: 0.0558 AC: 3680 AN: 65900

Other (OTH) AF: 0.0847 AC: 172 AN: 2030

Alfa AF: 0.0295 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;