rs4947490

chr7-55092845-A-Gchr7-55092845-A-T

Variant summary

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

The NM_005228.5(EGFR):c.89-49441A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,152 control chromosomes in the GnomAD database, including 37,020 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 0.69 (37020 hom., cov: 34)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.89-49441A>G		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.89-49441A>G		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105445 AN: 152034 Hom.: 36968 Cov.: 34

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.694 AC: 105557 AN: 152152 Hom.: 37020 Cov.: 34 AF XY: 0.699 AC XY: 51996 AN XY: 74378

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.727

Alfa AF: 0.692 Hom.: 72233

Bravo AF: 0.698

Asia WGS AF: 0.877 AC: 3048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.9
Dann	Benign	0.28

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: rs4947490; hg19: chr7-55160538;