Variant 7-55019062-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005228.5(EGFR):c.-216G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 265,078 control chromosomes in the GnomAD database, including 14,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6545 hom., cov: 33)

Exomes 𝑓: 0.35 ( 7521 hom. )

Consequence

EGFR
NM_005228.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.457

Variant links:

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]

EGFR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 7-55019062-G-T is Benign according to our data. Variant chr7-55019062-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1246877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5 linkuse as main transcript	c.-216G>T		5_prime_UTR_variant	1/28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 linkuse as main transcript	c.-216G>T		5_prime_UTR_variant	1/28	1	NM_005228.5	ENSP00000275493	P1	P00533-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

42919

AN:

150874

Hom.:

6550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.324

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.0472

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.348

AC:

39660

AN:

114100

Hom.:

7521

Cov.:

AF XY:

0.350

AC XY:

20618

AN XY:

58850

show subpopulations

Gnomad4 AFR exome

AF:

0.287

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.477

Gnomad4 EAS exome

AF:

0.0543

Gnomad4 SAS exome

AF:

0.386

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.284

AC:

42904

AN:

150978

Hom.:

6545

Cov.:

AF XY:

0.280

AC XY:

20669

AN XY:

73738

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.0475

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.109

Hom.:

190

Bravo

AF:

0.279

Asia WGS

AF:

0.181

AC:

622

AN:

3422

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	This variant is associated with the following publications: (PMID: 24137392, 16885506, 20621735, 15665278, 21292812) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Lung cancer

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over