rs2241055

Variant names:

• chr7-55172768-G-C
• rs2241055
• NM_005228.5:c.1920-215G>C

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.1920-215G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,371,538 control chromosomes in the GnomAD database, including 79,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7786 hom., cov: 33)
  • Exomes 𝑓: 0.34 (71944 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55
• Publications: 11 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=-1.06).
• BP6: Variant 7-55172768-G-C is Benign according to our data. Variant chr7-55172768-G-C is described in ClinVar as [Benign]. Clinvar id is 1286588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1920-215G>C		intron_variant	Intron 16 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.1920-215G>C		intron_variant	Intron 16 of 27	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000455089.5	c.1785-215G>C		intron_variant	Intron 15 of 25	1		ENSP00000415559.1
EGFR	ENST00000450046.2	c.1761-215G>C		intron_variant	Intron 16 of 27	4		ENSP00000413354.2
EGFR	ENST00000700145.1	c.267-215G>C		intron_variant	Intron 3 of 8			ENSP00000514824.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46673 AN: 152036 Hom.: 7783 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.337 AC: 411168 AN: 1219384 Hom.: 71944 AF XY: 0.339 AC XY: 206492 AN XY: 608784

African (AFR) AF: 0.194 AC: 5428 AN: 27962

American (AMR) AF: 0.329 AC: 11251 AN: 34206

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 10545 AN: 23852

East Asian (EAS) AF: 0.594 AC: 20603 AN: 34698

South Asian (SAS) AF: 0.389 AC: 29079 AN: 74678

European-Finnish (FIN) AF: 0.381 AC: 12642 AN: 33144

Middle Eastern (MID) AF: 0.410 AC: 2201 AN: 5372

European-Non Finnish (NFE) AF: 0.322 AC: 300831 AN: 933060

Other (OTH) AF: 0.355 AC: 18588 AN: 52412

GnomAD4 genome AF: 0.307 AC: 46690 AN: 152154 Hom.: 7786 Cov.: 33 AF XY: 0.315 AC XY: 23402 AN XY: 74382

African (AFR) AF: 0.195 AC: 8106 AN: 41524

American (AMR) AF: 0.322 AC: 4924 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2874 AN: 5174

South Asian (SAS) AF: 0.404 AC: 1949 AN: 4820

European-Finnish (FIN) AF: 0.391 AC: 4129 AN: 10572

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22140 AN: 67996

Other (OTH) AF: 0.325 AC: 686 AN: 2114

Alfa AF: 0.313 Hom.: 1003

Bravo AF: 0.300

Asia WGS AF: 0.451 AC: 1566 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 07, 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	-1.1
CADD	Benign	0.076
DANN	Benign	0.30
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: rs2241055; hg19: chr7-55240461; COSMIC: COSV99288772;