rs532284219

Variant names:

• chr11-65879879-TGCCTCCTG-T
• rs532284219
• NM_001335.4:c.29_36delTCCTGGCC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001335.4(CTSW):​c.29_36delTCCTGGCC​(p.Leu10ProfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,613,784 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (14 hom.)
• Consequence: CTSW NM_001335.4 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56
• Publications: 0 publications found

Genes affected

CTSW (HGNC:2546): (cathepsin W) The protein encoded by this gene, a member of the peptidase C1 family, is a cysteine proteinase that may have a specific function in the mechanism or regulation of T-cell cytolytic activity. The encoded protein is found associated with the membrane inside the endoplasmic reticulum of natural killer and cytotoxic T-cells. Expression of this gene is up-regulated by interleukin-2. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 11-65879879-TGCCTCCTG-T is Benign according to our data. Variant chr11-65879879-TGCCTCCTG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2641975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001335.4. 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
	CTSW	NM_001335.4	MANE Select	c.29_36delTCCTGGCC	p.Leu10ProfsTer15	frameshift	Exon 1 of 10	NP_001326.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSW	ENST00000307886.8	TSL:1 MANE Select	c.29_36delTCCTGGCC	p.Leu10ProfsTer15	frameshift	Exon 1 of 10	ENSP00000311300.3	P56202
	CTSW	ENST00000680443.1		c.29_36delTCCTGGCC	p.Leu10ProfsTer15	frameshift	Exon 1 of 10	ENSP00000505179.1	A0A7P0T8L7
	CTSW	ENST00000894913.1		c.29_36delTCCTGGCC	p.Leu10ProfsTer15	frameshift	Exon 1 of 10	ENSP00000564972.1

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152208 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00429

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00307 AC: 764 AN: 248856 AF XY: 0.00303

Gnomad AFR exome AF: 0.000932

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00751

Gnomad NFE exome AF: 0.00406

Gnomad OTH exome AF: 0.00412

GnomAD4 exome AF: 0.00379 AC: 5537 AN: 1461458 Hom.: 14 AF XY: 0.00385 AC XY: 2797 AN XY: 726992

African (AFR) AF: 0.000478 AC: 16 AN: 33472

American (AMR) AF: 0.00157 AC: 70 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00352 AC: 92 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00116 AC: 100 AN: 86182

European-Finnish (FIN) AF: 0.00730 AC: 389 AN: 53272

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.00423 AC: 4698 AN: 1111846

Other (OTH) AF: 0.00278 AC: 168 AN: 60384

GnomAD4 genome AF: 0.00306 AC: 466 AN: 152326 Hom.: 2 Cov.: 33 AF XY: 0.00315 AC XY: 235 AN XY: 74490

African (AFR) AF: 0.000842 AC: 35 AN: 41580

American (AMR) AF: 0.00203 AC: 31 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00706 AC: 75 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00429 AC: 292 AN: 68024

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00371 Hom.: 1

Bravo AF: 0.00248

EpiCase AF: 0.00393

EpiControl AF: 0.00439

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=120/80	disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs532284219; hg19: chr11-65647350; COSMIC: COSV57172897; COSMIC: COSV57172897;