7-55201223-C-T

Position:

chr7-55201223-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005228.5(EGFR):c.2982C>T(p.Asp994Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,614,064 control chromosomes in the GnomAD database, including 13,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1060 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12175 hom. )

Consequence

EGFR
NM_005228.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.403

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:

EGFR (HGNC:):

EGFR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 7-55201223-C-T is Benign according to our data. Variant chr7-55201223-C-T is described in ClinVar as [Benign]. Clinvar id is 259679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.403 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 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.2982C>T	p.Asp994Asp	synonymous_variant	25/28	ENST00000275493.7	NP_005219.2	P00533-1Q504U8F2YGG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 linkuse as main transcript	c.2982C>T	p.Asp994Asp	synonymous_variant	25/28	1	NM_005228.5	ENSP00000275493.2		P00533-1

Frequencies

GnomAD3 genomes

AF:

0.0997

AC:

15164

AN:

152072

Hom.:

1057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0273

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0936

GnomAD3 exomes

AF:

0.137

AC:

34569

AN:

251492

Hom.:

2977

AF XY:

0.141

AC XY:

19195

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.0731

Gnomad EAS exome

AF:

0.272

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.0996

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.118

AC:

172092

AN:

1461874

Hom.:

12175

Cov.:

AF XY:

0.120

AC XY:

87503

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0212

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.0742

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.0997

AC:

15168

AN:

152190

Hom.:

1060

Cov.:

AF XY:

0.109

AC XY:

8124

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0272

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.0726

Gnomad4 EAS

AF:

0.281

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.100

Gnomad4 OTH

AF:

0.0940

Alfa

AF:

0.0991

Hom.:

1331

Bravo

AF:

0.0910

Asia WGS

AF:

0.266

AC:

921

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

EGFR-related lung cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2024

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Lung cancer

Benign:1

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

-0.37

CADD

Benign

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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