7-55037627-A-G

Variant names:

• chr7-55037627-A-G
• rs12718939
• NM_005228.5:c.88+18262A>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+18262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,072 control chromosomes in the GnomAD database, including 42,986 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 0.75 (42986 hom., cov: 31)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 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.88+18262A>G		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.88+18262A>G		intron	N/A	NP_001333828.1
	EGFR	NM_001346898.2		c.88+18262A>G		intron	N/A	NP_001333827.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.88+18262A>G		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.88+18262A>G		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.88+18262A>G		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113740 AN: 151952 Hom.: 42918 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.749 AC: 113875 AN: 152072 Hom.: 42986 Cov.: 31 AF XY: 0.754 AC XY: 56033 AN XY: 74332

African (AFR) AF: 0.819 AC: 33956 AN: 41482

American (AMR) AF: 0.795 AC: 12149 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2492 AN: 3470

East Asian (EAS) AF: 0.953 AC: 4929 AN: 5172

South Asian (SAS) AF: 0.731 AC: 3525 AN: 4824

European-Finnish (FIN) AF: 0.768 AC: 8118 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46301 AN: 67964

Other (OTH) AF: 0.741 AC: 1561 AN: 2108

Alfa AF: 0.699 Hom.: 35867

Bravo AF: 0.757

Asia WGS AF: 0.843 AC: 2932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.79
DANN	Benign	0.30
PhyloP100		-0.78
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: rs12718939; hg19: chr7-55105320;