rs2058502

chr7-55110176-C-T

Variant summary

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

The NM_005228.5(EGFR):c.89-32110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,992 control chromosomes in the GnomAD database, including 27,715 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 0.59 (27715 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.89-32110C>T		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.89-32110C>T		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89818 AN: 151876 Hom.: 27703 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.591 AC: 89871 AN: 151992 Hom.: 27715 Cov.: 32 AF XY: 0.597 AC XY: 44356 AN XY: 74306

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.561

Alfa AF: 0.510 Hom.: 28134

Bravo AF: 0.595

Asia WGS AF: 0.714 AC: 2485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.3
Dann	Benign	0.15

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: rs2058502; hg19: chr7-55177869;