7-55020559-TACACACACACACAC-TACACACACACACACACACACACACAC

Variant names:

• chr7-55020559-T-TACACACACACAC
• rs11568315
• NM_005228.5:c.88+1217_88+1228dupACACACACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005228.5(EGFR):​c.88+1217_88+1228dupACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• 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.

• 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+1217_88+1228dupACACACACACAC		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+1195insACACACACACAC		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

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

African (AFR) AF: 0.0173 AC: 677 AN: 39222

American (AMR) AF: 0.00686 AC: 101 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.0143 AC: 48 AN: 3366

East Asian (EAS) AF: 0.0179 AC: 87 AN: 4866

South Asian (SAS) AF: 0.0305 AC: 136 AN: 4456

European-Finnish (FIN) AF: 0.00349 AC: 33 AN: 9460

Middle Eastern (MID) AF: 0.00709 AC: 2 AN: 282

European-Non Finnish (NFE) AF: 0.00409 AC: 270 AN: 65934

Other (OTH) AF: 0.0108 AC: 22 AN: 2030

Alfa AF: 0.00177 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

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

Other links and lift over

dbSNP: rs11568315; hg19: chr7-55088252;