Variant rs45567233 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_001911.3(CTSG):c.374A>G(p.Asn125Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,613,820 control chromosomes in the GnomAD database, including 4,534 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.061 ( 342 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4192 hom. )

Consequence

CTSG
NM_001911.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0310

Variant links:

Genes affected

CTSG (HGNC:2532): (cathepsin G) The protein encoded by this gene, a member of the peptidase S1 protein family, is found in azurophil granules of neutrophilic polymorphonuclear leukocytes. The encoded protease has a specificity similar to that of chymotrypsin C, and may participate in the killing and digestion of engulfed pathogens, and in connective tissue remodeling at sites of inflammation. In addition, the encoded protein is antimicrobial, with bacteriocidal activity against S. aureus and N. gonorrhoeae. Transcript variants utilizing alternative polyadenylation signals exist for this gene. [provided by RefSeq, Sep 2014]

CTSG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003850907).

BP6

Variant 14-24574465-T-C is Benign according to our data. Variant chr14-24574465-T-C is described in ClinVar as [Benign]. Clinvar id is 402574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSG	NM_001911.3 link	c.374A>G	p.Asn125Ser	missense_variant	4/5	ENST00000216336.3	NP_001902.1	P08311
CTSG	XM_011536499.2 link	c.416A>G	p.Asn139Ser	missense_variant	4/5		XP_011534801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSG	ENST00000216336.3 link	c.374A>G	p.Asn125Ser	missense_variant	4/5	1	NM_001911.3	ENSP00000216336.2		P08311
CTSG	ENST00000552252.1 link	n.855A>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0613

AC:

9313

AN:

152004

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0314

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0718

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.0995

Gnomad FIN

AF:

0.0794

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0654

Gnomad OTH

AF:

0.0651

GnomAD3 exomes

AF:

0.0801

AC:

20015

AN:

249924

Hom.:

953

AF XY:

0.0795

AC XY:

10744

AN XY:

135070

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0363

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.0987

Gnomad FIN exome

AF:

0.0771

Gnomad NFE exome

AF:

0.0693

Gnomad OTH exome

AF:

0.0693

GnomAD4 exome

AF:

0.0711

AC:

103994

AN:

1461698

Hom.:

4192

Cov.:

AF XY:

0.0716

AC XY:

52067

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.0992

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.174

Gnomad4 SAS exome

AF:

0.0972

Gnomad4 FIN exome

AF:

0.0784

Gnomad4 NFE exome

AF:

0.0664

Gnomad4 OTH exome

AF:

0.0677

GnomAD4 genome

AF:

0.0613

AC:

9328

AN:

152122

Hom.:

342

Cov.:

AF XY:

0.0628

AC XY:

4675

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.0716

Gnomad4 ASJ

AF:

0.0406

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.0986

Gnomad4 FIN

AF:

0.0794

Gnomad4 NFE

AF:

0.0654

Gnomad4 OTH

AF:

0.0696

Alfa

AF:

0.0665

Hom.:

620

Bravo

AF:

0.0600

TwinsUK

AF:

0.0645

AC:

239

ALSPAC

AF:

0.0698

AC:

269

ESP6500AA

AF:

0.0311

AC:

137

ESP6500EA

AF:

0.0607

AC:

522

ExAC

AF:

0.0809

AC:

9821

Asia WGS

AF:

0.140

AC:

485

AN:

3478

EpiCase

AF:

0.0625

EpiControl

AF:

0.0628

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.4

DANN

Benign

0.37

DEOGEN2

Benign

0.26

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.64

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.26

REVEL

Benign

0.11

Sift

Benign

0.40

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.030

MPC

0.35

ClinPred

0.0059

GERP RS

0.13

Varity_R

0.15

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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