Genetic Variant CTSG:c.204-73G>A (chr14-24574883-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001911.3(CTSG):c.204-73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,595,872 control chromosomes in the GnomAD database, including 77,204 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6722 hom., cov: 31)

Exomes 𝑓: 0.31 ( 70482 hom. )

Consequence

CTSG
NM_001911.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.390

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSG	NM_001911.3 link	c.204-73G>A		intron_variant	Intron 2 of 4	ENST00000216336.3	NP_001902.1
CTSG	XM_011536499.2 link	c.246-73G>A		intron_variant	Intron 2 of 4		XP_011534801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSG	ENST00000216336.3 link	c.204-73G>A		intron_variant	Intron 2 of 4	1	NM_001911.3	ENSP00000216336.2
CTSG	ENST00000552252.1 link	n.612G>A		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40704

AN:

151782

Hom.:

6707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0971

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.301

GnomAD4 exome

AF:

0.305

AC:

440423

AN:

1443970

Hom.:

70482

Cov.:

AF XY:

0.302

AC XY:

217165

AN XY:

718692

show subpopulations

African (AFR)

AF:

0.0911

AC:

3025

AN:

33204

American (AMR)

AF:

0.592

AC:

26426

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

8364

AN:

25800

East Asian (EAS)

AF:

0.354

AC:

14007

AN:

39600

South Asian (SAS)

AF:

0.256

AC:

21945

AN:

85614

European-Finnish (FIN)

AF:

0.343

AC:

16606

AN:

48468

Middle Eastern (MID)

AF:

0.277

AC:

1153

AN:

4166

European-Non Finnish (NFE)

AF:

0.300

AC:

330542

AN:

1102704

Other (OTH)

AF:

0.307

AC:

18355

AN:

59808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

15570

31140

46710

62280

77850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10972

21944

32916

43888

54860

<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:

0.268

AC:

40733

AN:

151902

Hom.:

6722

Cov.:

AF XY:

0.277

AC XY:

20581

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.0970

AC:

4020

AN:

41446

American (AMR)

AF:

0.477

AC:

7293

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1105

AN:

3472

East Asian (EAS)

AF:

0.356

AC:

1827

AN:

5136

South Asian (SAS)

AF:

0.259

AC:

1249

AN:

4814

European-Finnish (FIN)

AF:

0.358

AC:

3777

AN:

10544

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.300

AC:

20367

AN:

67900

Other (OTH)

AF:

0.302

AC:

636

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1417

2834

4252

5669

7086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.273

Hom.:

1805

Bravo

AF:

0.273

Asia WGS

AF:

0.331

AC:

1152

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.3

(source)

DANN

Benign

0.39

PhyloP100

0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over