rs884419

chr7-55208587-G-Achr7-55208587-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.*2970G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,040 control chromosomes in the GnomAD database, including 1,439 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 (1438 hom., cov: 31)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.*2970G>A		3_prime_UTR_variant	28/28	ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.*2970G>A		3_prime_UTR_variant	28/28	1	NM_005228.5	P1
EGFR	ENST00000450046.2	c.*2970G>A		3_prime_UTR_variant	28/28	4

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17474 AN: 151900 Hom.: 1440 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.136 AC: 3 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.115 AC: 17481 AN: 152018 Hom.: 1438 Cov.: 31 AF XY: 0.119 AC XY: 8812 AN XY: 74302

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0807

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0973

Gnomad4 NFE AF: 0.0899

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0944 Hom.: 107

Bravo AF: 0.120

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.1
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: rs884419; hg19: chr7-55276280;