chr7-55127932-G-A

Variant names:

• chr7-55127932-G-A
• rs4947979
• NM_005228.5:c.89-14354G>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.89-14354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,184 control chromosomes in the GnomAD database, including 46,646 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 0.78 (46646 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 16 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-14354G>A		intron_variant	Intron 1 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.89-14354G>A		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118578 AN: 152066 Hom.: 46614 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.780 AC: 118651 AN: 152184 Hom.: 46646 Cov.: 33 AF XY: 0.786 AC XY: 58499 AN XY: 74386

African (AFR) AF: 0.687 AC: 28510 AN: 41506

American (AMR) AF: 0.831 AC: 12702 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2594 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5159 AN: 5188

South Asian (SAS) AF: 0.868 AC: 4186 AN: 4822

European-Finnish (FIN) AF: 0.826 AC: 8743 AN: 10588

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 54014 AN: 68002

Other (OTH) AF: 0.795 AC: 1678 AN: 2112

Alfa AF: 0.788 Hom.: 93773

Bravo AF: 0.777

Asia WGS AF: 0.902 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		1.1
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: rs4947979; hg19: chr7-55195625;