rs2983301

Positions:

• chr20-23505952-T-C

Variant summary

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

The XM_047439815.1(CST8):​c.*435-823T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,844 control chromosomes in the GnomAD database, including 22,926 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 0.54 (22926 hom., cov: 31)
• Consequence: CST8 XM_047439815.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705

Genes affected

CST8 (HGNC:2480): (cystatin 8) 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. 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 protein similar to type 2 cystatins. The encoded protein exhibits highly tissue-specific expression in the reproductive tract, suggesting implicit roles in reproduction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ENSG00000260202 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CST8	XM_047439815.1	c.*435-823T>C		intron_variant			XP_047295771.1
CST8	XM_047439816.1	c.*435-823T>C		intron_variant			XP_047295772.1
CST8	XM_047439817.1	c.*435-823T>C		intron_variant			XP_047295773.1
CST8	XM_047439820.1	c.*66-823T>C		intron_variant			XP_047295776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000260202	ENST00000619495.1	n.438+12665A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82178 AN: 151726 Hom.: 22903 Cov.: 31

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.542 AC: 82258 AN: 151844 Hom.: 22926 Cov.: 31 AF XY: 0.535 AC XY: 39709 AN XY: 74216

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.519

Alfa AF: 0.523 Hom.: 9896

Bravo AF: 0.538

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2983301; hg19: chr20-23486589;