Variant rs17337107 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.2184+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 1,614,116 control chromosomes in the GnomAD database, including 1,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 107 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1728 hom. )

Consequence

EGFR
NM_005228.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.42

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=-0.75).

BP6

Variant 7-55174062-G-A is Benign according to our data. Variant chr7-55174062-G-A is described in ClinVar as [Benign]. Clinvar id is 1251320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.2184+19G>A		intron_variant		ENST00000275493.7	NP_005219.2	P00533-1Q504U8F2YGG7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
EGFR	ENST00000275493.7 link	c.2184+19G>A	intron_variant	1	NM_005228.5	ENSP00000275493.2	P00533-1
EGFR	ENST00000455089.5 link	c.2049+19G>A	intron_variant	1		ENSP00000415559.1	Q504U8
EGFR	ENST00000450046.2 link	c.2025+19G>A	intron_variant	4		ENSP00000413354.2	C9JYS6
EGFR	ENST00000700145.1 link	c.531+19G>A	intron_variant			ENSP00000514824.1	A0A8V8TPW8

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4599

AN:

152242

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00909

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.0424

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0582

Gnomad FIN

AF:

0.0251

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0463

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0361

AC:

9054

AN:

250792

Hom.:

223

AF XY:

0.0394

AC XY:

5352

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00681

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0378

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0676

Gnomad FIN exome

AF:

0.0236

Gnomad NFE exome

AF:

0.0462

Gnomad OTH exome

AF:

0.0381

GnomAD4 exome

AF:

0.0454

AC:

66374

AN:

1461756

Hom.:

1728

Cov.:

AF XY:

0.0464

AC XY:

33754

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00654

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.0406

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0694

Gnomad4 FIN exome

AF:

0.0255

Gnomad4 NFE exome

AF:

0.0489

Gnomad4 OTH exome

AF:

0.0407

GnomAD4 genome

AF:

0.0302

AC:

4601

AN:

152360

Hom.:

107

Cov.:

AF XY:

0.0299

AC XY:

2231

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00906

Gnomad4 AMR

AF:

0.0182

Gnomad4 ASJ

AF:

0.0424

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0584

Gnomad4 FIN

AF:

0.0251

Gnomad4 NFE

AF:

0.0463

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0378

Hom.:

Bravo

AF:

0.0278

Asia WGS

AF:

0.0250

AC:

AN:

3472

ClinVar

Significance: 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 07, 2019	- -

EGFR-related lung cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.58

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

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