rs726217

Variant names:

• chr20-23603479-G-A
• rs726217
• NM_001008693.3:c.*31C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CST9	NM_001008693.3	c.*31C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000376971.4	NP_001008693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CST9	ENST00000376971.4	c.*31C>T		3_prime_UTR_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.585 AC: 140693 AN: 240430 AF XY: 0.588

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 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

African (AFR) AF: 0.159 AC: 5315 AN: 33382

American (AMR) AF: 0.651 AC: 28516 AN: 43778

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 15815 AN: 25932

East Asian (EAS) AF: 0.693 AC: 27441 AN: 39588

South Asian (SAS) AF: 0.510 AC: 43692 AN: 85694

European-Finnish (FIN) AF: 0.660 AC: 35096 AN: 53144

Middle Eastern (MID) AF: 0.643 AC: 3699 AN: 5754

European-Non Finnish (NFE) AF: 0.604 AC: 669398 AN: 1108706

Other (OTH) AF: 0.587 AC: 35298 AN: 60174

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

African (AFR) AF: 0.178 AC: 7398 AN: 41464

American (AMR) AF: 0.627 AC: 9573 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3466

East Asian (EAS) AF: 0.691 AC: 3540 AN: 5126

South Asian (SAS) AF: 0.489 AC: 2359 AN: 4820

European-Finnish (FIN) AF: 0.666 AC: 7049 AN: 10582

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.605 AC: 41096 AN: 67944

Other (OTH) AF: 0.525 AC: 1105 AN: 2106

Alfa AF: 0.574 Hom.: 37164

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
PhyloP100		0.43
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: rs726217; hg19: chr20-23584116; COSMIC: COSV65402497;