7-55160480-C-T

Variant names:

• chr7-55160480-C-T
• rs759162
• NM_005228.5:c.1498+142C>T

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.1498+142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 903,888 control chromosomes in the GnomAD database, including 255,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41496 hom., cov: 34)
  • Exomes 𝑓: 0.75 (214126 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.564
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-55160480-C-T is Benign according to our data. Variant chr7-55160480-C-T is described in ClinVar as Benign. ClinVar VariationId is 1274112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1498+142C>T		intron_variant	Intron 12 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.1498+142C>T		intron_variant	Intron 12 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111754 AN: 152084 Hom.: 41462 Cov.: 34

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.750 AC: 563526 AN: 751686 Hom.: 214126 AF XY: 0.755 AC XY: 289965 AN XY: 384106

African (AFR) AF: 0.661 AC: 11776 AN: 17802

American (AMR) AF: 0.841 AC: 18279 AN: 21732

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 14337 AN: 18198

East Asian (EAS) AF: 0.998 AC: 32067 AN: 32144

South Asian (SAS) AF: 0.878 AC: 47962 AN: 54646

European-Finnish (FIN) AF: 0.710 AC: 22124 AN: 31166

Middle Eastern (MID) AF: 0.798 AC: 2131 AN: 2672

European-Non Finnish (NFE) AF: 0.721 AC: 387370 AN: 537208

Other (OTH) AF: 0.761 AC: 27480 AN: 36118

GnomAD4 genome AF: 0.735 AC: 111844 AN: 152202 Hom.: 41496 Cov.: 34 AF XY: 0.742 AC XY: 55194 AN XY: 74412

African (AFR) AF: 0.667 AC: 27684 AN: 41520

American (AMR) AF: 0.808 AC: 12353 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2756 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5170 AN: 5184

South Asian (SAS) AF: 0.889 AC: 4293 AN: 4830

European-Finnish (FIN) AF: 0.718 AC: 7599 AN: 10580

Middle Eastern (MID) AF: 0.839 AC: 245 AN: 292

European-Non Finnish (NFE) AF: 0.728 AC: 49492 AN: 68004

Other (OTH) AF: 0.756 AC: 1600 AN: 2116

Alfa AF: 0.734 Hom.: 23311

Bravo AF: 0.740

Asia WGS AF: 0.928 AC: 3230 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.41
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs759162; hg19: chr7-55228173;