rs6593205

Positions:

• chr7-55100999-A-G

Variant summary

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

The NM_005228.5(EGFR):​c.89-41287A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,206 control chromosomes in the GnomAD database, including 35,919 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 0.68 (35919 hom., cov: 34)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.89-41287A>G		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.89-41287A>G		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103549 AN: 152088 Hom.: 35901 Cov.: 34

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.681 AC: 103614 AN: 152206 Hom.: 35919 Cov.: 34 AF XY: 0.684 AC XY: 50892 AN XY: 74410

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.663

Alfa AF: 0.650 Hom.: 8240

Bravo AF: 0.687

Asia WGS AF: 0.774 AC: 2691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.25

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: rs6593205; hg19: chr7-55168692;