7-55157447-G-C

Variant names:

• chr7-55157447-G-C
• rs13222549
• NM_005228.5:c.1208-216G>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.1208-216G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,236 control chromosomes in the GnomAD database, including 7,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7474 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.18
• Publications: 10 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=-0.89).
• BP6: Variant 7-55157447-G-C is Benign according to our data. Variant chr7-55157447-G-C is described in ClinVar as Benign. ClinVar VariationId is 1246809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1208-216G>C		intron_variant	Intron 10 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.1208-216G>C		intron_variant	Intron 10 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46541 AN: 152118 Hom.: 7482 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.306 AC: 46545 AN: 152236 Hom.: 7474 Cov.: 33 AF XY: 0.297 AC XY: 22100 AN XY: 74438

African (AFR) AF: 0.265 AC: 11021 AN: 41518

American (AMR) AF: 0.285 AC: 4369 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3472

East Asian (EAS) AF: 0.111 AC: 577 AN: 5180

South Asian (SAS) AF: 0.191 AC: 922 AN: 4826

European-Finnish (FIN) AF: 0.269 AC: 2855 AN: 10608

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24579 AN: 68002

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.208 Hom.: 446

Bravo AF: 0.305

Asia WGS AF: 0.168 AC: 586 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.42
PhyloP100		-2.2
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: rs13222549; hg19: chr7-55225140;