rs45567233

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

19 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CTSG	NM_001911.3 link	c.374A>G	p.Asn125Ser	missense_variant	Exon 4 of 5	ENST00000216336.3	NP_001902.1
CTSG	XM_011536499.2 link	c.416A>G	p.Asn139Ser	missense_variant	Exon 4 of 5		XP_011534801.1

Ensembl

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

GnomAD2 exomes

AF:

0.0801

AC:

20015

AN:

249924

AF XY:

0.0795

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 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

African (AFR)

AF:

0.0291

AC:

974

AN:

33480

American (AMR)

AF:

0.0992

AC:

4437

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

912

AN:

26136

East Asian (EAS)

AF:

0.174

AC:

6896

AN:

39700

South Asian (SAS)

AF:

0.0972

AC:

8382

AN:

86258

European-Finnish (FIN)

AF:

0.0784

AC:

4174

AN:

53232

Middle Eastern (MID)

AF:

0.0433

AC:

250

AN:

5768

European-Non Finnish (NFE)

AF:

0.0664

AC:

73881

AN:

1112004

Other (OTH)

AF:

0.0677

AC:

4088

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

5991

11982

17972

23963

29954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2832

5664

8496

11328

14160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0613

AC:

9328

AN:

152122

Hom.:

342

Cov.:

AF XY:

0.0628

AC XY:

4675

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0316

AC:

1313

AN:

41508

American (AMR)

AF:

0.0716

AC:

1095

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0406

AC:

141

AN:

3470

East Asian (EAS)

AF:

0.157

AC:

806

AN:

5140

South Asian (SAS)

AF:

0.0986

AC:

473

AN:

4798

European-Finnish (FIN)

AF:

0.0794

AC:

842

AN:

10602

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0654

AC:

4444

AN:

67992

Other (OTH)

AF:

0.0696

AC:

147

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

465

930

1396

1861

2326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0652

Hom.:

813

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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

PhyloP100

-0.031

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over