rs9642391

Variant names:

• chr7-55177671-G-C
• rs9642391
• NM_005228.5:c.2283+2851G>C

Variant summary

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

The NM_005228.5(EGFR):​c.2283+2851G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,146 control chromosomes in the GnomAD database, including 5,992 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 (5992 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 10 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 = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.2283+2851G>C		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.2148+2851G>C		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.2124+2851G>C		intron	N/A	NP_001333829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2283+2851G>C		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.2148+2851G>C		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000450046.2	TSL:4	c.2124+2851G>C		intron	N/A	ENSP00000413354.2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38569 AN: 152028 Hom.: 5994 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.254 AC: 38569 AN: 152146 Hom.: 5992 Cov.: 32 AF XY: 0.263 AC XY: 19572 AN XY: 74380

African (AFR) AF: 0.0966 AC: 4013 AN: 41552

American (AMR) AF: 0.298 AC: 4555 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3472

East Asian (EAS) AF: 0.614 AC: 3168 AN: 5156

South Asian (SAS) AF: 0.384 AC: 1849 AN: 4812

European-Finnish (FIN) AF: 0.373 AC: 3943 AN: 10568

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18920 AN: 67978

Other (OTH) AF: 0.266 AC: 561 AN: 2110

Alfa AF: 0.258 Hom.: 717

Bravo AF: 0.245

Asia WGS AF: 0.465 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.31
DANN	Benign	0.60
PhyloP100		-1.2
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: rs9642391; hg19: chr7-55245364;