NM_001911.3:c.44G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001911.3(CTSG):c.44G>C(p.Gly15Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,610,484 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G15R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.015 ( 57 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 39 hom. )

Consequence

CTSG
NM_001911.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.688

Publications

1 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=0.0033926964).

BP6

Variant 14-24576180-C-G is Benign according to our data. Variant chr14-24576180-C-G is described in ClinVar as Benign. ClinVar VariationId is 776828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2214/152230) while in subpopulation AFR AF = 0.0506 (2103/41532). AF 95% confidence interval is 0.0488. There are 57 homozygotes in GnomAd4. There are 1048 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 57 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001911.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSG	NM_001911.3	MANE Select	c.44G>C	p.Gly15Ala	missense	Exon 1 of 5	NP_001902.1	P08311

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTSG	ENST00000216336.3	TSL:1 MANE Select	c.44G>C	p.Gly15Ala	missense	Exon 1 of 5	ENSP00000216336.2	P08311
CTSG	ENST00000871534.1		c.44G>C	p.Gly15Ala	missense	Exon 1 of 5	ENSP00000541593.1
CTSG	ENST00000552252.1	TSL:2	n.71G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2211

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00373

AC:

910

AN:

244130

AF XY:

0.00277

show subpopulations

Gnomad AFR exome

AF:

0.0513

Gnomad AMR exome

AF:

0.00274

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000905

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.00144

AC:

2094

AN:

1458254

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

934

AN XY:

724842

show subpopulations

African (AFR)

AF:

0.0497

AC:

1661

AN:

33442

American (AMR)

AF:

0.00318

AC:

141

AN:

44326

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.0000941

AC:

AN:

84998

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53226

Middle Eastern (MID)

AF:

0.00209

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000648

AC:

AN:

1110574

Other (OTH)

AF:

0.00332

AC:

200

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

191

286

382

477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0145

AC:

2214

AN:

152230

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1048

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0506

AC:

2103

AN:

41532

American (AMR)

AF:

0.00471

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68016

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

185

278

370

463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00253

Hom.:

Bravo

AF:

0.0168

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0517

AC:

228

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00456

AC:

553

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.2

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.32

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.95

PhyloP100

0.69

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.16

Sift

Uncertain

0.027

Sift4G

Benign

0.38

Polyphen

0.12

Vest4

0.098

MVP

0.91

MPC

1.3

ClinPred

0.020

GERP RS

1.1

PromoterAI

0.16

Neutral

(source)

Varity_R

0.089

gMVP

0.67

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over