7-55093350-G-C

Variant names:

• chr7-55093350-G-C
• rs4947972
• NM_005228.5:c.89-48936G>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.89-48936G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,186 control chromosomes in the GnomAD database, including 7,011 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 (7011 hom., cov: 34)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 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.89-48936G>C		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.89-48936G>C		intron	N/A	NP_001333828.1
	EGFR	NM_001346898.2		c.89-48936G>C		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.89-48936G>C		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.89-48936G>C		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.89-48936G>C		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39197 AN: 152068 Hom.: 7003 Cov.: 34

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.258 AC: 39209 AN: 152186 Hom.: 7011 Cov.: 34 AF XY: 0.270 AC XY: 20062 AN XY: 74382

African (AFR) AF: 0.0834 AC: 3464 AN: 41542

American (AMR) AF: 0.395 AC: 6045 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3470

East Asian (EAS) AF: 0.862 AC: 4462 AN: 5176

South Asian (SAS) AF: 0.373 AC: 1802 AN: 4828

European-Finnish (FIN) AF: 0.348 AC: 3677 AN: 10564

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18000 AN: 67986

Other (OTH) AF: 0.261 AC: 551 AN: 2112

Alfa AF: 0.134 Hom.: 263

Bravo AF: 0.260

Asia WGS AF: 0.543 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		0.77
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: rs4947972; hg19: chr7-55161043;