rs884225

chr7-55206391-T-Cchr7-55206391-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005228.5(EGFR):c.*774T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 233,320 control chromosomes in the GnomAD database, including 2,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1226 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1256 hom.)
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-55206391-T-C is Benign according to our data. Variant chr7-55206391-T-C is described in ClinVar as [Benign]. Clinvar id is 1253347.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.*774T>C		3_prime_UTR_variant	28/28	ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.*774T>C		3_prime_UTR_variant	28/28	1	NM_005228.5	P1
EGFR	ENST00000450046.2	c.*774T>C		3_prime_UTR_variant	28/28	4
EGFR	ENST00000700146.1	n.2151T>C		non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15265 AN: 152116 Hom.: 1228 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0897

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.139 AC: 11289 AN: 81086 Hom.: 1256 Cov.: 0 AF XY: 0.137 AC XY: 5097 AN XY: 37272

Gnomad4 AFR exome AF: 0.0670

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0814

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.0932

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.100 AC: 15266 AN: 152234 Hom.: 1226 Cov.: 32 AF XY: 0.104 AC XY: 7743 AN XY: 74438

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.0983

Gnomad4 ASJ AF: 0.0809

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.0897

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0746 Hom.: 236

Bravo AF: 0.103

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2020

This variant is associated with the following publications: (PMID: 25925667, 30470824, 23028094) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.4
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs884225; hg19: chr7-55274084;