rs3752651

Positions:

• chr7-55161850-T-C

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.1631+219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,250 control chromosomes in the GnomAD database, including 1,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1980 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.261

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=-0.82).
• BP6: Variant 7-55161850-T-C is Benign according to our data. Variant chr7-55161850-T-C is described in ClinVar as [Benign]. Clinvar id is 1225850.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.1631+219T>C		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.1631+219T>C		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23047 AN: 152132 Hom.: 1982 Cov.: 33

Gnomad AFR AF: 0.0738

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.151 AC: 23036 AN: 152250 Hom.: 1980 Cov.: 33 AF XY: 0.147 AC XY: 10949 AN XY: 74446

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.177

Alfa AF: 0.193 Hom.: 4038

Bravo AF: 0.154

Asia WGS AF: 0.122 AC: 427 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	-0.82
CADD	Benign	4.3
DANN	Benign	0.70

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: rs3752651; hg19: chr7-55229543; COSMIC: COSV51773959; COSMIC: COSV51773959;