rs2293348

Positions:

• chr7-55199064-C-T

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.2848+201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,192 control chromosomes in the GnomAD database, including 5,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5626 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.558

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=-0.86).
• BP6: Variant 7-55199064-C-T is Benign according to our data. Variant chr7-55199064-C-T is described in ClinVar as [Benign]. Clinvar id is 1227710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2848+201C>T		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2848+201C>T		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39131 AN: 152074 Hom.: 5615 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.257 AC: 39159 AN: 152192 Hom.: 5626 Cov.: 33 AF XY: 0.254 AC XY: 18894 AN XY: 74398

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.292

Alfa AF: 0.313 Hom.: 10762

Bravo AF: 0.264

Asia WGS AF: 0.235 AC: 819 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

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.59

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: rs2293348; hg19: chr7-55266757; COSMIC: COSV51774039;