rs2983301

Variant names:

• chr20-23505952-T-C
• rs2983301
• ENST00000619495.1:n.438+12665A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000619495.1(ENSG00000260202):​n.438+12665A>G 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: ENSG00000260202 ENST00000619495.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 3 publications found

Genes affected

ENSG00000260202 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000619495.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000260202	ENST00000619495.1	TSL:4	n.438+12665A>G		intron	N/A
	ENSG00000295999	ENST00000734924.1		n.322-823T>C		intron	N/A

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

African (AFR) AF: 0.646 AC: 26727 AN: 41376

American (AMR) AF: 0.490 AC: 7478 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3468

East Asian (EAS) AF: 0.198 AC: 1021 AN: 5164

South Asian (SAS) AF: 0.421 AC: 2022 AN: 4808

European-Finnish (FIN) AF: 0.591 AC: 6200 AN: 10498

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35587 AN: 67954

Other (OTH) AF: 0.519 AC: 1089 AN: 2100

Alfa AF: 0.524 Hom.: 11101

Bravo AF: 0.538

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.43
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs2983301; hg19: chr20-23486589;