rs13247687

chr7-55134083-G-Achr7-55134083-G-C

Variant summary

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

The NM_005228.5(EGFR):c.89-8203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,046 control chromosomes in the GnomAD database, including 14,206 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 0.42 (14206 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.89-8203G>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.89-8203G>A		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63570 AN: 151928 Hom.: 14223 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.418 AC: 63559 AN: 152046 Hom.: 14206 Cov.: 32 AF XY: 0.426 AC XY: 31624 AN XY: 74320

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.419

Alfa AF: 0.275 Hom.: 669

Bravo AF: 0.406

Asia WGS AF: 0.487 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.2
Dann	Benign	0.88

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: rs13247687; hg19: chr7-55201776;