7-55101219-C-T

Variant names:

• chr7-55101219-C-T
• rs4947974
• NM_005228.5:c.89-41067C>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.89-41067C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,154 control chromosomes in the GnomAD database, including 7,753 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 0.29 (7753 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 5 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 = 0.674 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.89-41067C>T		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.89-41067C>T		intron	N/A	NP_001333828.1
	EGFR	NM_001346898.2		c.89-41067C>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.89-41067C>T		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.89-41067C>T		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.89-41067C>T		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44321 AN: 152036 Hom.: 7764 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.291 AC: 44303 AN: 152154 Hom.: 7753 Cov.: 33 AF XY: 0.302 AC XY: 22468 AN XY: 74384

African (AFR) AF: 0.136 AC: 5671 AN: 41552

American (AMR) AF: 0.362 AC: 5541 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3568 AN: 5152

South Asian (SAS) AF: 0.365 AC: 1759 AN: 4814

European-Finnish (FIN) AF: 0.402 AC: 4251 AN: 10582

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21510 AN: 67984

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.247 Hom.: 1060

Bravo AF: 0.282

Asia WGS AF: 0.465 AC: 1618 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	1.2
DANN	Benign	0.55
PhyloP100		-0.64
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: rs4947974; hg19: chr7-55168912;