chr7-55113749-G-A

Variant names:

• chr7-55113749-G-A
• rs759160
• NM_005228.5:c.89-28537G>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.89-28537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,182 control chromosomes in the GnomAD database, including 41,540 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 0.73 (41540 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.89-28537G>A		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.89-28537G>A		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.-72+3791G>A		intron	N/A	NP_001333829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.89-28537G>A		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.89-28537G>A		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.89-28537G>A		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111640 AN: 152064 Hom.: 41516 Cov.: 33

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.734 AC: 111716 AN: 152182 Hom.: 41540 Cov.: 33 AF XY: 0.736 AC XY: 54772 AN XY: 74400

African (AFR) AF: 0.632 AC: 26212 AN: 41480

American (AMR) AF: 0.788 AC: 12059 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2658 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5175 AN: 5190

South Asian (SAS) AF: 0.902 AC: 4352 AN: 4824

European-Finnish (FIN) AF: 0.709 AC: 7507 AN: 10594

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51142 AN: 68002

Other (OTH) AF: 0.760 AC: 1606 AN: 2114

Alfa AF: 0.751 Hom.: 71074

Bravo AF: 0.735

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.023
DANN	Benign	0.26
PhyloP100		-3.0
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: rs759160; hg19: chr7-55181442;