rs3800827

Variant names:

• chr7-55074961-A-G
• rs3800827
• NM_005228.5:c.88+55596A>G

Variant summary

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

The NM_005228.5(EGFR):​c.88+55596A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,136 control chromosomes in the GnomAD database, including 6,655 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 0.25 (6655 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+55596A>G		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+55596A>G		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38371 AN: 152018 Hom.: 6662 Cov.: 33

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.252 AC: 38358 AN: 152136 Hom.: 6655 Cov.: 33 AF XY: 0.265 AC XY: 19721 AN XY: 74350

African (AFR) AF: 0.0888 AC: 3691 AN: 41548

American (AMR) AF: 0.330 AC: 5047 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3472

East Asian (EAS) AF: 0.875 AC: 4538 AN: 5186

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4814

European-Finnish (FIN) AF: 0.392 AC: 4131 AN: 10544

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17328 AN: 67986

Other (OTH) AF: 0.247 AC: 521 AN: 2108

Alfa AF: 0.236 Hom.: 634

Bravo AF: 0.243

Asia WGS AF: 0.552 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.61
PhyloP100		-0.91
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: rs3800827; hg19: chr7-55142654;