Variant 20-23750828-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001898.3(CST1):c.39C>T(p.Ala13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000488 in 1,613,670 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

CST1
NM_001898.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.984

Variant links:

Genes affected

CST1 (HGNC:2473): (cystatin SN) 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 cysteine proteinase inhibitor found in saliva, tears, urine, and seminal fluid. [provided by RefSeq, Jul 2008]

CST1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 20-23750828-G-A is Benign according to our data. Variant chr20-23750828-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025369.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.984 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CST1	NM_001898.3 linkuse as main transcript	c.39C>T	p.Ala13=	synonymous_variant	1/3	ENST00000304749.7	NP_001889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CST1	ENST00000304749.7 linkuse as main transcript	c.39C>T	p.Ala13=	synonymous_variant	1/3	1	NM_001898.3	ENSP00000305731	P1
CST1	ENST00000398402.1 linkuse as main transcript	c.39C>T	p.Ala13=	synonymous_variant	2/4	5		ENSP00000381439	P1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000699

AC:

175

AN:

250378

Hom.:

AF XY:

0.000672

AC XY:

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000857

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000474

AC:

693

AN:

1461388

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

353

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000452

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000624

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000523

Hom.:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

CST1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.54

DANN

Benign

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over