7-55157477-G-C

Variant names:

• chr7-55157477-G-C
• rs4947987
• NM_005228.5:c.1208-186G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005228.5(EGFR):​c.1208-186G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,268 control chromosomes in the GnomAD database, including 58,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.88 (58534 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-55157477-G-C is Benign according to our data. Variant chr7-55157477-G-C is described in ClinVar as Benign. ClinVar VariationId is 1276071.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.1208-186G>C		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.1073-186G>C		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.1049-186G>C		intron	N/A	NP_001333829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.1208-186G>C		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.1073-186G>C		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.1208-186G>C		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133218 AN: 152150 Hom.: 58500 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.896

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

GnomAD4 genome AF: 0.875 AC: 133306 AN: 152268 Hom.: 58534 Cov.: 33 AF XY: 0.876 AC XY: 65186 AN XY: 74450

African (AFR) AF: 0.823 AC: 34163 AN: 41532

American (AMR) AF: 0.914 AC: 14000 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3186 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5184

South Asian (SAS) AF: 0.954 AC: 4608 AN: 4828

European-Finnish (FIN) AF: 0.861 AC: 9131 AN: 10606

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.884 AC: 60121 AN: 68014

Other (OTH) AF: 0.897 AC: 1899 AN: 2116

Alfa AF: 0.869 Hom.: 7166

Bravo AF: 0.877

Asia WGS AF: 0.975 AC: 3392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.22
DANN	Benign	0.40
PhyloP100		-1.6
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: rs4947987; hg19: chr7-55225170;