14-24573714-C-T

Variant names:

• chr14-24573714-C-T
• NM_001911.3:c.691G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001911.3(CTSG):​c.691G>A​(p.Val231Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CTSG NM_001911.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1496321).
• BP6: Variant 14-24573714-C-T is Benign according to our data. Variant chr14-24573714-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3837333.Status of the report is criteria_provided_single_submitter, 1 stars.

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.691G>A	p.Val231Ile	missense	Exon 5 of 5	NP_001902.1	P08311

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSG	ENST00000216336.3	TSL:1 MANE Select	c.691G>A	p.Val231Ile	missense	Exon 5 of 5	ENSP00000216336.2	P08311
	CTSG	ENST00000871534.1		c.733G>A	p.Val245Ile	missense	Exon 5 of 5	ENSP00000541593.1
	CTSG	ENST00000552252.1	TSL:2	n.1172G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.010
DANN	Benign	0.34
DEOGEN2	Benign	0.36	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.28	T
MutationAssessor	Benign	-0.040	N
PhyloP100		-1.4
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.12	N
REVEL	Uncertain	0.32
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.71		Loss of MoRF binding (P = 0.134)
MVP		0.64
MPC		0.37
ClinPred		0.039	T
GERP RS		-6.0
Varity_R		0.055
gMVP		0.57
Mutation Taster		=94/6	polymorphism

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

hg19: chr14-25042920;