chr7-55111707-T-G

Variant names:

• chr7-55111707-T-G
• rs759159
• NM_005228.5:c.89-30579T>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.89-30579T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,860 control chromosomes in the GnomAD database, including 25,829 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 0.56 (25829 hom., cov: 31)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 13 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: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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.89-30579T>G		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.89-30579T>G		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.-72+1749T>G		intron	N/A	NP_001333829.1	C9JYS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.89-30579T>G		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.89-30579T>G		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000344576.7	TSL:1	c.89-30579T>G		intron	N/A	ENSP00000345973.2	P00533-3

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85564 AN: 151740 Hom.: 25814 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.564 AC: 85608 AN: 151860 Hom.: 25829 Cov.: 31 AF XY: 0.571 AC XY: 42383 AN XY: 74210

African (AFR) AF: 0.359 AC: 14834 AN: 41358

American (AMR) AF: 0.672 AC: 10265 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1719 AN: 3468

East Asian (EAS) AF: 0.994 AC: 5140 AN: 5170

South Asian (SAS) AF: 0.697 AC: 3357 AN: 4814

European-Finnish (FIN) AF: 0.633 AC: 6677 AN: 10542

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41648 AN: 67910

Other (OTH) AF: 0.567 AC: 1197 AN: 2112

Alfa AF: 0.600 Hom.: 78821

Bravo AF: 0.559

Asia WGS AF: 0.812 AC: 2825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.72
PhyloP100		-0.15
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: rs759159; hg19: chr7-55179400;