7-55151466-C-T

Variant names:

• chr7-55151466-C-T
• rs2075110
• NM_005228.5:c.628+104C>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.628+104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,206,082 control chromosomes in the GnomAD database, including 170,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22580 hom., cov: 32)
  • Exomes 𝑓: 0.53 (147824 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.900
• Publications: 26 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=-0.87).
• BP6: Variant 7-55151466-C-T is Benign according to our data. Variant chr7-55151466-C-T is described in ClinVar as Benign. ClinVar VariationId is 1233950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.628+104C>T		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.628+104C>T		intron_variant	Intron 5 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82212 AN: 151918 Hom.: 22533 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.526 AC: 554643 AN: 1054044 Hom.: 147824 AF XY: 0.527 AC XY: 284835 AN XY: 540832

African (AFR) AF: 0.623 AC: 15821 AN: 25388

American (AMR) AF: 0.531 AC: 21700 AN: 40858

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 13185 AN: 23270

East Asian (EAS) AF: 0.333 AC: 12358 AN: 37148

South Asian (SAS) AF: 0.564 AC: 43093 AN: 76356

European-Finnish (FIN) AF: 0.494 AC: 24492 AN: 49606

Middle Eastern (MID) AF: 0.538 AC: 2035 AN: 3784

European-Non Finnish (NFE) AF: 0.529 AC: 397181 AN: 750960

Other (OTH) AF: 0.531 AC: 24778 AN: 46674

GnomAD4 genome AF: 0.541 AC: 82328 AN: 152038 Hom.: 22580 Cov.: 32 AF XY: 0.535 AC XY: 39775 AN XY: 74302

African (AFR) AF: 0.620 AC: 25714 AN: 41480

American (AMR) AF: 0.506 AC: 7731 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1820 AN: 5154

South Asian (SAS) AF: 0.556 AC: 2670 AN: 4802

European-Finnish (FIN) AF: 0.482 AC: 5084 AN: 10554

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35659 AN: 67974

Other (OTH) AF: 0.529 AC: 1116 AN: 2108

Alfa AF: 0.515 Hom.: 9885

Bravo AF: 0.546

Asia WGS AF: 0.481 AC: 1673 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	-0.87
CADD	Benign	1.0
DANN	Benign	0.32
PhyloP100		-0.90
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: rs2075110; hg19: chr7-55219159; COSMIC: COSV99286433; COSMIC: COSV99286433;