Variant rs11506105 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.629-62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,463,048 control chromosomes in the GnomAD database, including 246,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26081 hom., cov: 32)

Exomes 𝑓: 0.58 ( 220309 hom. )

Consequence

EGFR
NM_005228.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.19

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=-0.95).

BP6

Variant 7-55152484-A-G is Benign according to our data. Variant chr7-55152484-A-G is described in ClinVar as [Benign]. Clinvar id is 1277571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.629-62A>G		intron_variant		ENST00000275493.7	NP_005219.2	P00533-1Q504U8F2YGG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 link	c.629-62A>G		intron_variant		1	NM_005228.5	ENSP00000275493.2		P00533-1

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

88559

AN:

151928

Hom.:

26040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.642

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.580

GnomAD4 exome

AF:

0.577

AC:

756264

AN:

1311002

Hom.:

220309

Cov.:

AF XY:

0.577

AC XY:

381421

AN XY:

660530

show subpopulations

Gnomad4 AFR exome

AF:

0.651

Gnomad4 AMR exome

AF:

0.572

Gnomad4 ASJ exome

AF:

0.639

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.602

Gnomad4 FIN exome

AF:

0.539

Gnomad4 NFE exome

AF:

0.582

Gnomad4 OTH exome

AF:

0.582

GnomAD4 genome

AF:

0.583

AC:

88667

AN:

152046

Hom.:

26081

Cov.:

AF XY:

0.576

AC XY:

42821

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.642

Gnomad4 AMR

AF:

0.549

Gnomad4 ASJ

AF:

0.639

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.591

Gnomad4 FIN

AF:

0.529

Gnomad4 NFE

AF:

0.578

Gnomad4 OTH

AF:

0.584

Alfa

AF:

0.579

Hom.:

29764

Bravo

AF:

0.587

Asia WGS

AF:

0.501

AC:

1746

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Mar 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.012

DANN

Benign

0.49

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