rs1357973

chr7-55211587-C-Achr7-55211587-C-Gchr7-55211587-C-T

Variant summary

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

The NM_005228.5(EGFR):c.*5970C>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 0.906 in 152,254 control chromosomes in the GnomAD database, including 62,586 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 0.91 (62586 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.*5970C>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.*5970C>A		3_prime_UTR_variant	28/28	1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137750 AN: 152136 Hom.: 62526 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.899

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.906 AC: 137869 AN: 152254 Hom.: 62586 Cov.: 33 AF XY: 0.910 AC XY: 67733 AN XY: 74448

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.867

Gnomad4 OTH AF: 0.899

Alfa AF: 0.885 Hom.: 7416

Bravo AF: 0.909

Asia WGS AF: 0.933 AC: 3236 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.066
Dann	Benign	0.42

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: rs1357973; hg19: chr7-55279280;