NM_005228.5:c.88+50830G>A

Variant names:

• chr7-55070195-G-A
• rs1344307
• NM_005228.5:c.88+50830G>A

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+50830G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,234 control chromosomes in the GnomAD database, including 56,170 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 (56170 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 9 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+50830G>A		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+50830G>A		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130268 AN: 152116 Hom.: 56109 Cov.: 32

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.856 AC: 130387 AN: 152234 Hom.: 56170 Cov.: 32 AF XY: 0.861 AC XY: 64039 AN XY: 74420

African (AFR) AF: 0.943 AC: 39157 AN: 41544

American (AMR) AF: 0.861 AC: 13172 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2722 AN: 3470

East Asian (EAS) AF: 0.974 AC: 5044 AN: 5180

South Asian (SAS) AF: 0.843 AC: 4053 AN: 4808

European-Finnish (FIN) AF: 0.861 AC: 9126 AN: 10600

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

European-Non Finnish (NFE) AF: 0.800 AC: 54426 AN: 68024

Other (OTH) AF: 0.837 AC: 1765 AN: 2108

Alfa AF: 0.817 Hom.: 26006

Bravo AF: 0.861

Asia WGS AF: 0.911 AC: 3167 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	0.63
DANN	Benign	0.38
PhyloP100		-0.047
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: rs1344307; hg19: chr7-55137888;