NM_005228.5:c.89-7381G>A

Variant names:

• chr7-55134905-G-A
• rs17172446
• NM_005228.5:c.89-7381G>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.89-7381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,978 control chromosomes in the GnomAD database, including 4,642 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 0.24 (4642 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 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.89-7381G>A		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.89-7381G>A		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.-71-7381G>A		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.89-7381G>A		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.89-7381G>A		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000344576.7	TSL:1	c.89-7381G>A		intron	N/A	ENSP00000345973.2	P00533-3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36306 AN: 151860 Hom.: 4622 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0276

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.239 AC: 36372 AN: 151978 Hom.: 4642 Cov.: 32 AF XY: 0.237 AC XY: 17578 AN XY: 74282

African (AFR) AF: 0.272 AC: 11279 AN: 41436

American (AMR) AF: 0.293 AC: 4482 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.0277 AC: 143 AN: 5168

South Asian (SAS) AF: 0.196 AC: 941 AN: 4792

European-Finnish (FIN) AF: 0.182 AC: 1923 AN: 10560

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16070 AN: 67964

Other (OTH) AF: 0.251 AC: 530 AN: 2110

Alfa AF: 0.235 Hom.: 19316

Bravo AF: 0.251

Asia WGS AF: 0.166 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.43
PhyloP100		-1.4
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: rs17172446; hg19: chr7-55202598;