rs2075109

chr7-55151210-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.560-84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,315,558 control chromosomes in the GnomAD database, including 184,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (20952 hom., cov: 33)
  • Exomes 𝑓: 0.53 (163138 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08

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=-0.91).
• BP6: Variant 7-55151210-T-C is Benign according to our data. Variant chr7-55151210-T-C is described in ClinVar as [Benign]. Clinvar id is 1265640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.560-84T>C		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.560-84T>C		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79418 AN: 151996 Hom.: 20916 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.527 AC: 613507 AN: 1163444 Hom.: 163138 AF XY: 0.528 AC XY: 313572 AN XY: 593832

Gnomad4 AFR exome AF: 0.556

Gnomad4 AMR exome AF: 0.529

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.565

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.523 AC: 79520 AN: 152114 Hom.: 20952 Cov.: 33 AF XY: 0.517 AC XY: 38454 AN XY: 74350

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.518

Alfa AF: 0.527 Hom.: 6068

Bravo AF: 0.524

Asia WGS AF: 0.475 AC: 1655 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.080
Dann	Benign	0.29

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: rs2075109; hg19: chr7-55218903; COSMIC: COSV51801153; COSMIC: COSV51801153;