rs11506105

Variant names:

• chr7-55152484-A-G
• rs11506105
• NM_005228.5:c.629-62A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005228.5(EGFR):​c.629-62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,463,048 control chromosomes in the GnomAD database, including 246,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26081 hom., cov: 32)
  • Exomes 𝑓: 0.58 (220309 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.19
• Publications: 41 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-55152484-A-G is Benign according to our data. Variant chr7-55152484-A-G is described in ClinVar as Benign. ClinVar VariationId is 1277571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.629-62A>G		intron_variant	Intron 5 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.629-62A>G		intron_variant	Intron 5 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88559 AN: 151928 Hom.: 26040 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.577 AC: 756264 AN: 1311002 Hom.: 220309 Cov.: 20 AF XY: 0.577 AC XY: 381421 AN XY: 660530

African (AFR) AF: 0.651 AC: 19901 AN: 30570

American (AMR) AF: 0.572 AC: 25522 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 16083 AN: 25182

East Asian (EAS) AF: 0.329 AC: 12807 AN: 38970

South Asian (SAS) AF: 0.602 AC: 50106 AN: 83258

European-Finnish (FIN) AF: 0.539 AC: 28480 AN: 52852

Middle Eastern (MID) AF: 0.631 AC: 3461 AN: 5488

European-Non Finnish (NFE) AF: 0.582 AC: 567679 AN: 974712

Other (OTH) AF: 0.582 AC: 32225 AN: 55390

GnomAD4 genome AF: 0.583 AC: 88667 AN: 152046 Hom.: 26081 Cov.: 32 AF XY: 0.576 AC XY: 42821 AN XY: 74328

African (AFR) AF: 0.642 AC: 26641 AN: 41472

American (AMR) AF: 0.549 AC: 8398 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1789 AN: 5146

South Asian (SAS) AF: 0.591 AC: 2851 AN: 4826

European-Finnish (FIN) AF: 0.529 AC: 5585 AN: 10556

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39297 AN: 67970

Other (OTH) AF: 0.584 AC: 1233 AN: 2112

Alfa AF: 0.579 Hom.: 43765

Bravo AF: 0.587

Asia WGS AF: 0.501 AC: 1746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 29, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.012
DANN	Benign	0.49
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: rs11506105; hg19: chr7-55220177; COSMIC: COSV51766104;