rs2236742

Variant names:

• chr14-24575924-C-T
• rs2236742
• NM_001911.3:c.55+245G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001911.3(CTSG):​c.55+245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,192 control chromosomes in the GnomAD database, including 1,850 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 0.15 (1850 hom., cov: 32)
• Consequence: CTSG NM_001911.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 13 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSG	NM_001911.3	c.55+245G>A		intron_variant	Intron 1 of 4	ENST00000216336.3	NP_001902.1
CTSG	XM_011536499.2	c.55+245G>A		intron_variant	Intron 1 of 4		XP_011534801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSG	ENST00000216336.3	c.55+245G>A		intron_variant	Intron 1 of 4	1	NM_001911.3	ENSP00000216336.2
CTSG	ENST00000552252.1	n.82+245G>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23259 AN: 152074 Hom.: 1840 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23296 AN: 152192 Hom.: 1850 Cov.: 32 AF XY: 0.154 AC XY: 11475 AN XY: 74408

African (AFR) AF: 0.132 AC: 5469 AN: 41512

American (AMR) AF: 0.142 AC: 2168 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3472

East Asian (EAS) AF: 0.201 AC: 1039 AN: 5178

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4826

European-Finnish (FIN) AF: 0.160 AC: 1695 AN: 10578

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10904 AN: 68014

Other (OTH) AF: 0.173 AC: 366 AN: 2114

Alfa AF: 0.160 Hom.: 6179

Bravo AF: 0.151

Asia WGS AF: 0.224 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.41
PhyloP100		-1.7
PromoterAI		-0.029	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236742; hg19: chr14-25045130;