rs6954351

Positions:

• chr7-55103497-G-A

Variant summary

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

The NM_005228.5(EGFR):​c.89-38789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,214 control chromosomes in the GnomAD database, including 1,085 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 0.11 (1085 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-38789G>A		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.89-38789G>A		intron_variant		1	NM_005228.5	ENSP00000275493	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16256 AN: 152096 Hom.: 1087 Cov.: 33

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.107 AC: 16253 AN: 152214 Hom.: 1085 Cov.: 33 AF XY: 0.105 AC XY: 7795 AN XY: 74406

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0704

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.135

Alfa AF: 0.140 Hom.: 2412

Bravo AF: 0.105

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.51

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: rs6954351; hg19: chr7-55171190;