rs17172432

Positions:

• chr7-55073624-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.88+54259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,172 control chromosomes in the GnomAD database, including 9,148 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 0.30 (9148 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+54259T>C		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.88+54259T>C		intron_variant		1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45764 AN: 152054 Hom.: 9112 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.301 AC: 45872 AN: 152172 Hom.: 9148 Cov.: 33 AF XY: 0.298 AC XY: 22188 AN XY: 74396

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0911

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.258

Alfa AF: 0.251 Hom.: 2116

Bravo AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs17172432; hg19: chr7-55141317;