7-55067126-A-G

Variant names:

• chr7-55067126-A-G
• rs723526
• NM_005228.5:c.88+47761A>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.88+47761A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,208 control chromosomes in the GnomAD database, including 56,206 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 0.86 (56206 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+47761A>G		intron_variant	Intron 1 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.88+47761A>G		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130298 AN: 152090 Hom.: 56144 Cov.: 33

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.857 AC: 130418 AN: 152208 Hom.: 56206 Cov.: 33 AF XY: 0.861 AC XY: 64071 AN XY: 74424

African (AFR) AF: 0.944 AC: 39185 AN: 41520

American (AMR) AF: 0.862 AC: 13184 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2699 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5029 AN: 5166

South Asian (SAS) AF: 0.845 AC: 4079 AN: 4828

European-Finnish (FIN) AF: 0.861 AC: 9131 AN: 10602

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54421 AN: 68008

Other (OTH) AF: 0.839 AC: 1768 AN: 2108

Alfa AF: 0.831 Hom.: 6563

Bravo AF: 0.861

Asia WGS AF: 0.913 AC: 3174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.43
PhyloP100		-1.5
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: rs723526; hg19: chr7-55134819;