rs2070697

Positions:

• chr14-24574883-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CTSG	NM_001911.3	c.204-73G>A		intron_variant		ENST00000216336.3
CTSG	XM_011536499.2	c.246-73G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSG	ENST00000216336.3	c.204-73G>A		intron_variant		1	NM_001911.3	P1
CTSG	ENST00000552252.1	n.612G>A		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40704 AN: 151782 Hom.: 6707 Cov.: 31

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.: 29 AF XY: 0.302 AC XY: 217165 AN XY: 718692

Gnomad4 AFR exome AF: 0.0911

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.268 AC: 40733 AN: 151902 Hom.: 6722 Cov.: 31 AF XY: 0.277 AC XY: 20581 AN XY: 74224

Gnomad4 AFR AF: 0.0970

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.302

Alfa AF: 0.248 Hom.: 808

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
DANN	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs2070697; hg19: chr14-25044089; COSMIC: COSV53537183;