7-55027504-A-G

Position:

• chr7-55027504-A-G

Variant summary

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

The ENST00000275493.7(EGFR):​c.88+8139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,090 control chromosomes in the GnomAD database, including 27,388 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 (27388 hom., cov: 33)
• Consequence: EGFR ENST00000275493.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

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 = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+8139A>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.88+8139A>G		intron_variant		1	NM_005228.5	ENSP00000275493	P1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90149 AN: 151974 Hom.: 27339 Cov.: 33

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.593 AC: 90256 AN: 152090 Hom.: 27388 Cov.: 33 AF XY: 0.599 AC XY: 44534 AN XY: 74362

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.538

Alfa AF: 0.533 Hom.: 28149

Bravo AF: 0.605

Asia WGS AF: 0.678 AC: 2358 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	5.8
DANN	Benign	0.58

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: rs763317; hg19: chr7-55095197;