rs6593211

Positions:

• chr7-55210271-G-A
• chr7-55210271-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.*4654G>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 0.378 in 152,004 control chromosomes in the GnomAD database, including 12,583 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 0.38 (12583 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.*4654G>A		3_prime_UTR_variant	28/28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.*4654G>A		3_prime_UTR_variant	28/28	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000450046.2	c.*4654G>A		3_prime_UTR_variant	28/28	4		ENSP00000413354.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57341 AN: 151882 Hom.: 12551 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.378 AC: 57422 AN: 152002 Hom.: 12583 Cov.: 33 AF XY: 0.386 AC XY: 28670 AN XY: 74300

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.343

Alfa AF: 0.284 Hom.: 11270

Bravo AF: 0.384

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.084
DANN	Benign	0.22

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: rs6593211; hg19: chr7-55277964;