7-55067179-A-G

Variant names:

• chr7-55067179-A-G
• rs723527
• NM_005228.5:c.88+47814A>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+47814A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 149,834 control chromosomes in the GnomAD database, including 22,202 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 0.53 (22202 hom., cov: 34)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 33 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.88+47814A>G		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.88+47814A>G		intron	N/A	NP_001333828.1
	EGFR	NM_001346898.2		c.88+47814A>G		intron	N/A	NP_001333827.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.88+47814A>G		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.88+47814A>G		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.88+47814A>G		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 79453 AN: 149718 Hom.: 22153 Cov.: 34

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.531 AC: 79559 AN: 149834 Hom.: 22202 Cov.: 34 AF XY: 0.543 AC XY: 39811 AN XY: 73304

African (AFR) AF: 0.655 AC: 25749 AN: 39310

American (AMR) AF: 0.584 AC: 8880 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1250 AN: 3468

East Asian (EAS) AF: 0.965 AC: 5001 AN: 5182

South Asian (SAS) AF: 0.613 AC: 2960 AN: 4830

European-Finnish (FIN) AF: 0.592 AC: 6262 AN: 10578

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27907 AN: 67986

Other (OTH) AF: 0.486 AC: 1008 AN: 2076

Alfa AF: 0.440 Hom.: 19561

Bravo AF: 0.530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.37
PhyloP100		-1.2
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: rs723527; hg19: chr7-55134872;