rs11766798

chr7-55056626-G-Achr7-55056626-G-T

Variant summary

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

The NM_005228.5(EGFR):c.88+37261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,140 control chromosomes in the GnomAD database, including 6,922 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 0.26 (6922 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+37261G>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+37261G>A		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39225 AN: 152022 Hom.: 6927 Cov.: 33

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.258 AC: 39210 AN: 152140 Hom.: 6922 Cov.: 33 AF XY: 0.270 AC XY: 20112 AN XY: 74384

Gnomad4 AFR AF: 0.0903

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.255

Alfa AF: 0.253 Hom.: 694

Bravo AF: 0.252

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.0
Dann	Benign	0.68

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: rs11766798; hg19: chr7-55124319;