rs726217

Positions:

• chr20-23603479-G-A
• chr20-23603479-G-C

Variant summary

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

The NM_001008693.3(CST9):​c.*31C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,608,140 control chromosomes in the GnomAD database, including 282,424 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 0.49 (21513 hom., cov: 32)
  • Exomes 𝑓: 0.59 (260911 hom.)
• Consequence: CST9 NM_001008693.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

Genes affected

CST9 (HGNC:13261): (cystatin 9) The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a secreted protein that may play a role in hematopoietic differentiation or inflammation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CST9	NM_001008693.3	c.*31C>T		3_prime_UTR_variant	2/2	ENST00000376971.4	NP_001008693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CST9	ENST00000376971.4	c.*31C>T		3_prime_UTR_variant	2/2	1	NM_001008693.3	ENSP00000366170.4

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75042 AN: 151870 Hom.: 21509 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.529

GnomAD3 exomes AF: 0.585 AC: 140693 AN: 240430 Hom.: 42723 AF XY: 0.588 AC XY: 76354 AN XY: 129824

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.655

Gnomad ASJ exome AF: 0.612

Gnomad EAS exome AF: 0.688

Gnomad SAS exome AF: 0.505

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.611

Gnomad OTH exome AF: 0.603

GnomAD4 exome AF: 0.594 AC: 864270 AN: 1456152 Hom.: 260911 Cov.: 52 AF XY: 0.592 AC XY: 428782 AN XY: 723798

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.651

Gnomad4 ASJ exome AF: 0.610

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.510

Gnomad4 FIN exome AF: 0.660

Gnomad4 NFE exome AF: 0.604

Gnomad4 OTH exome AF: 0.587

GnomAD4 genome AF: 0.494 AC: 75054 AN: 151988 Hom.: 21513 Cov.: 32 AF XY: 0.501 AC XY: 37221 AN XY: 74290

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.525

Alfa AF: 0.588 Hom.: 26990

Bravo AF: 0.480

Asia WGS AF: 0.554 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs726217; hg19: chr20-23584116; COSMIC: COSV65402497;