rs9692301

Variant names:

• chr7-55176061-A-G
• rs9692301
• NM_005228.5:c.2283+1241A>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.2283+1241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,214 control chromosomes in the GnomAD database, including 5,662 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 0.26 (5662 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2283+1241A>G		intron_variant	Intron 19 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2283+1241A>G		intron_variant	Intron 19 of 27	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000455089.5	c.2148+1241A>G		intron_variant	Intron 18 of 25	1		ENSP00000415559.1
EGFR	ENST00000450046.2	c.2124+1241A>G		intron_variant	Intron 19 of 27	4		ENSP00000413354.2
EGFR	ENST00000700145.1	c.630+1241A>G		intron_variant	Intron 6 of 8			ENSP00000514824.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39532 AN: 152096 Hom.: 5650 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.260 AC: 39569 AN: 152214 Hom.: 5662 Cov.: 33 AF XY: 0.254 AC XY: 18915 AN XY: 74410

African (AFR) AF: 0.190 AC: 7911 AN: 41530

American (AMR) AF: 0.346 AC: 5290 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3470

East Asian (EAS) AF: 0.0162 AC: 84 AN: 5190

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4818

European-Finnish (FIN) AF: 0.205 AC: 2173 AN: 10592

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20986 AN: 68014

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.292 Hom.: 22060

Bravo AF: 0.269

Asia WGS AF: 0.148 AC: 515 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.64
PhyloP100		0.20
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: rs9692301; hg19: chr7-55243754; COSMIC: COSV51773967;