NM_005228.5:c.89-55598G>A

Variant names:

• chr7-55086688-G-A
• rs12535536
• NM_005228.5:c.89-55598G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.89-55598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,202 control chromosomes in the GnomAD database, including 47,227 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (47227 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-55598G>A		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.89-55598G>A		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118914 AN: 152084 Hom.: 47162 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.782 AC: 119037 AN: 152202 Hom.: 47227 Cov.: 33 AF XY: 0.787 AC XY: 58550 AN XY: 74410

African (AFR) AF: 0.900 AC: 37374 AN: 41544

American (AMR) AF: 0.825 AC: 12614 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2580 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4998 AN: 5178

South Asian (SAS) AF: 0.739 AC: 3567 AN: 4826

European-Finnish (FIN) AF: 0.773 AC: 8186 AN: 10584

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.695 AC: 47227 AN: 67980

Other (OTH) AF: 0.773 AC: 1635 AN: 2116

Alfa AF: 0.721 Hom.: 98742

Bravo AF: 0.795

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs12535536; hg19: chr7-55154381;