Variant rs2070856 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001898.3(CST1):c.92C>T(p.Pro31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,842 control chromosomes in the GnomAD database, including 19,097 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2045 hom., cov: 31)

Exomes 𝑓: 0.14 ( 17052 hom. )

Consequence

CST1
NM_001898.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039392084).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CST1	NM_001898.3 link	c.92C>T	p.Pro31Leu	missense_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.92C>T	p.Pro31Leu	missense_variant	1/3	1	NM_001898.3	ENSP00000305731.2		P01037
CST1	ENST00000398402.1 link	c.92C>T	p.Pro31Leu	missense_variant	2/4	5		ENSP00000381439.1		P01037

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23516

AN:

152004

Hom.:

2041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.0901

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.0711

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.145

AC:

36354

AN:

251334

Hom.:

3311

AF XY:

0.154

AC XY:

20881

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.0636

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.0752

Gnomad SAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.144

AC:

211180

AN:

1461718

Hom.:

17052

Cov.:

AF XY:

0.149

AC XY:

108333

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.0660

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.0751

Gnomad4 SAS exome

AF:

0.303

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.155

AC:

23538

AN:

152124

Hom.:

2045

Cov.:

AF XY:

0.156

AC XY:

11593

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.0901

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.0708

Gnomad4 SAS

AF:

0.312

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.128

Hom.:

3058

Bravo

AF:

0.148

TwinsUK

AF:

0.135

AC:

499

ALSPAC

AF:

0.146

AC:

563

ESP6500AA

AF:

0.206

AC:

908

ESP6500EA

AF:

0.135

AC:

1157

ExAC

AF:

0.151

AC:

18376

Asia WGS

AF:

0.237

AC:

824

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.061

DANN

Benign

0.51

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00030

LIST_S2

Benign

0.24

.;T

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.79

N;N

REVEL

Benign

0.034

Sift

Benign

0.34

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0030

B;B

Vest4

0.026

MPC

0.0034

ClinPred

0.0025

GERP RS

-2.9

Varity_R

0.035

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over