7-55084193-G-T

Variant names:

• chr7-55084193-G-T
• rs7780270
• NM_005228.5:c.89-58093G>T

Variant summary

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

The NM_005228.5(EGFR):​c.89-58093G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,076 control chromosomes in the GnomAD database, including 21,943 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 0.53 (21943 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 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.89-58093G>T		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.89-58093G>T		intron	N/A	NP_001333828.1
	EGFR	NM_001346898.2		c.89-58093G>T		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.89-58093G>T		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.89-58093G>T		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.89-58093G>T		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80235 AN: 151958 Hom.: 21934 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.528 AC: 80278 AN: 152076 Hom.: 21943 Cov.: 33 AF XY: 0.537 AC XY: 39949 AN XY: 74340

African (AFR) AF: 0.502 AC: 20805 AN: 41454

American (AMR) AF: 0.606 AC: 9271 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1455 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4766 AN: 5170

South Asian (SAS) AF: 0.602 AC: 2903 AN: 4824

European-Finnish (FIN) AF: 0.616 AC: 6519 AN: 10576

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32971 AN: 67978

Other (OTH) AF: 0.493 AC: 1037 AN: 2104

Alfa AF: 0.494 Hom.: 41221

Bravo AF: 0.530

Asia WGS AF: 0.714 AC: 2485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.69
PhyloP100		-0.55
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: rs7780270; hg19: chr7-55151886;