Variant 20-23750840-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001898.3(CST1):c.27G>A(p.Leu9Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,613,098 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 2 hom. )

Consequence

CST1
NM_001898.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.449

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 20-23750840-C-T is Benign according to our data. Variant chr20-23750840-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025024.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.449 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CST1	NM_001898.3 link	c.27G>A	p.Leu9Leu	synonymous_variant	1/3	ENST00000304749.7	NP_001889.2	P01037

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CST1	ENST00000304749.7 link	c.27G>A	p.Leu9Leu	synonymous_variant	1/3	1	NM_001898.3	ENSP00000305731.2		P01037
CST1	ENST00000398402.1 link	c.27G>A	p.Leu9Leu	synonymous_variant	2/4	5		ENSP00000381439.1		P01037

Frequencies

GnomAD3 genomes

AF:

0.000716

AC:

109

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000793

AC:

197

AN:

248316

Hom.:

AF XY:

0.000760

AC XY:

102

AN XY:

134228

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.000321

Gnomad ASJ exome

AF:

0.00200

Gnomad EAS exome

AF:

0.000165

Gnomad SAS exome

AF:

0.000594

Gnomad FIN exome

AF:

0.0000933

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.000658

GnomAD4 exome

AF:

0.000576

AC:

842

AN:

1460814

Hom.:

Cov.:

AF XY:

0.000626

AC XY:

455

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000627

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000574

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000722

AC:

110

AN:

152284

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000610

Hom.:

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

-0.88

CADD

Benign

4.7

DANN

Benign

0.63

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