rs2241054

Variant names:

• chr7-55172286-G-A
• rs2241054
• NM_005228.5:c.1920-697G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55172286-G-A
• chr7-55172286-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.1920-697G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,108 control chromosomes in the GnomAD database, including 5,297 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5297 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1920-697G>A		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.1920-697G>A		intron_variant	Intron 16 of 27	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000455089.5	c.1785-697G>A		intron_variant	Intron 15 of 25	1		ENSP00000415559.1
EGFR	ENST00000450046.2	c.1761-697G>A		intron_variant	Intron 16 of 27	4		ENSP00000413354.2
EGFR	ENST00000700145.1	c.267-697G>A		intron_variant	Intron 3 of 8			ENSP00000514824.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36588 AN: 151990 Hom.: 5295 Cov.: 33

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.241 AC: 36595 AN: 152108 Hom.: 5297 Cov.: 33 AF XY: 0.248 AC XY: 18420 AN XY: 74338

African (AFR) AF: 0.0923 AC: 3831 AN: 41496

American (AMR) AF: 0.274 AC: 4182 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2868 AN: 5184

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4812

European-Finnish (FIN) AF: 0.311 AC: 3278 AN: 10552

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18560 AN: 68000

Other (OTH) AF: 0.253 AC: 532 AN: 2106

Alfa AF: 0.271 Hom.: 3129

Bravo AF: 0.234

Asia WGS AF: 0.422 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.064
DANN	Benign	0.53
PhyloP100		-0.41
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: rs2241054; hg19: chr7-55239979;