chr7-55106649-C-A

Variant names:

• chr7-55106649-C-A
• rs2330951
• NM_005228.5:c.89-35637C>A

Variant summary

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

The NM_005228.5(EGFR):​c.89-35637C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,172 control chromosomes in the GnomAD database, including 49,622 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 0.80 (49622 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 11 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=-1.08).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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.89-35637C>A		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.89-35637C>A		intron	N/A	NP_001333828.1
	EGFR	NM_001346898.2		c.89-35637C>A		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.89-35637C>A		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.89-35637C>A		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.89-35637C>A		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122337 AN: 152054 Hom.: 49589 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.805 AC: 122424 AN: 152172 Hom.: 49622 Cov.: 32 AF XY: 0.808 AC XY: 60094 AN XY: 74402

African (AFR) AF: 0.876 AC: 36382 AN: 41542

American (AMR) AF: 0.766 AC: 11701 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3017 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5149 AN: 5176

South Asian (SAS) AF: 0.894 AC: 4303 AN: 4814

European-Finnish (FIN) AF: 0.743 AC: 7867 AN: 10590

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51288 AN: 67980

Other (OTH) AF: 0.819 AC: 1729 AN: 2110

Alfa AF: 0.773 Hom.: 87918

Bravo AF: 0.807

Asia WGS AF: 0.922 AC: 3204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.049
DANN	Benign	0.18
PhyloP100		-1.4
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: rs2330951; hg19: chr7-55174342;