chr7-55177814-A-G

Variant names:

• chr7-55177814-A-G
• rs845552
• NM_005228.5:c.2283+2994A>G

Variant summary

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

The NM_005228.5(EGFR):​c.2283+2994A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,142 control chromosomes in the GnomAD database, including 15,344 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 0.44 (15344 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 16 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2283+2994A>G		intron_variant	Intron 19 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2283+2994A>G		intron_variant	Intron 19 of 27	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000455089.5	c.2148+2994A>G		intron_variant	Intron 18 of 25	1		ENSP00000415559.1
EGFR	ENST00000450046.2	c.2124+2994A>G		intron_variant	Intron 19 of 27	4		ENSP00000413354.2
EGFR	ENST00000700145.1	c.630+2994A>G		intron_variant	Intron 6 of 8			ENSP00000514824.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66750 AN: 152024 Hom.: 15344 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.439 AC: 66767 AN: 152142 Hom.: 15344 Cov.: 33 AF XY: 0.442 AC XY: 32849 AN XY: 74382

African (AFR) AF: 0.310 AC: 12885 AN: 41512

American (AMR) AF: 0.431 AC: 6597 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3466

East Asian (EAS) AF: 0.621 AC: 3211 AN: 5174

South Asian (SAS) AF: 0.449 AC: 2167 AN: 4826

European-Finnish (FIN) AF: 0.545 AC: 5768 AN: 10580

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32718 AN: 67970

Other (OTH) AF: 0.462 AC: 975 AN: 2112

Alfa AF: 0.463 Hom.: 13294

Bravo AF: 0.429

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.36
PhyloP100		1.0
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: rs845552; hg19: chr7-55245507;