Variant chr7-55019446-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.88+81G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 918,674 control chromosomes in the GnomAD database, including 10,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1639 hom., cov: 33)

Exomes 𝑓: 0.15 ( 9058 hom. )

Consequence

EGFR
NM_005228.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.295

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=-0.56).

BP6

Variant 7-55019446-G-T is Benign according to our data. Variant chr7-55019446-G-T is described in ClinVar as [Benign]. Clinvar id is 1263180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.185 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.88+81G>T		intron_variant		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.88+81G>T		intron_variant		1	NM_005228.5	ENSP00000275493	P1	P00533-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21778

AN:

150848

Hom.:

1635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.0321

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.00217

Gnomad SAS

AF:

0.0491

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.0757

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.119

GnomAD4 exome

AF:

0.148

AC:

113646

AN:

767718

Hom.:

9058

AF XY:

0.149

AC XY:

55221

AN XY:

371462

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.000817

Gnomad4 SAS exome

AF:

0.0613

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.144

AC:

21813

AN:

150956

Hom.:

1639

Cov.:

AF XY:

0.146

AC XY:

10738

AN XY:

73756

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.00218

Gnomad4 SAS

AF:

0.0490

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.142

Hom.:

182

Bravo

AF:

0.146

Asia WGS

AF:

0.0500

AC:

173

AN:

3448

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	clinical testing	GeneDx	Feb 11, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.95

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