rs4947488

Positions:

• chr7-55048862-T-A
• chr7-55048862-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.88+29497T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,118 control chromosomes in the GnomAD database, including 6,865 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 (6865 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+29497T>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+29497T>A		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39375 AN: 152000 Hom.: 6867 Cov.: 32

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.259 AC: 39368 AN: 152118 Hom.: 6865 Cov.: 32 AF XY: 0.271 AC XY: 20169 AN XY: 74364

Gnomad4 AFR AF: 0.0906

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.263

Alfa AF: 0.151 Hom.: 308

Bravo AF: 0.253

Asia WGS AF: 0.540 AC: 1878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.77

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: rs4947488; hg19: chr7-55116555;