7-55111707-T-G

Position:

• chr7-55111707-T-G

Variant summary

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

The NM_005228.5(EGFR):​c.89-30579T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,860 control chromosomes in the GnomAD database, including 25,829 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 0.56 (25829 hom., cov: 31)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-30579T>G		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.89-30579T>G		intron_variant		1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85564 AN: 151740 Hom.: 25814 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.564 AC: 85608 AN: 151860 Hom.: 25829 Cov.: 31 AF XY: 0.571 AC XY: 42383 AN XY: 74210

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.567

Alfa AF: 0.596 Hom.: 37505

Bravo AF: 0.559

Asia WGS AF: 0.812 AC: 2825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.72

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: rs759159; hg19: chr7-55179400;