Variant chr20-23443976-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000347397.5(CSTL1):c.262T>C(p.Trp88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,612,164 control chromosomes in the GnomAD database, including 224,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.59 ( 28176 hom., cov: 33)

Exomes 𝑓: 0.51 ( 196011 hom. )

Consequence

CSTL1
ENST00000347397.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

Variant links:

Genes affected

CSTL1 (HGNC:15958): (cystatin like 1) 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 at the telomeric end of the cystatin locus and encodes a type 2 cystatin-like protein. The specific function of this protein has not been determined. [provided by RefSeq, Jul 2008]

CSTL1 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=3.3079068E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSTL1	NM_138283.1 linkuse as main transcript	c.262T>C	p.Trp88Arg	missense_variant	3/4	ENST00000347397.5	NP_612140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSTL1	ENST00000347397.5 linkuse as main transcript	c.262T>C	p.Trp88Arg	missense_variant	3/4	1	NM_138283.1	ENSP00000344907	P1
CSTL1	ENST00000246020.3 linkuse as main transcript	c.262T>C	p.Trp88Arg	missense_variant	3/4	1		ENSP00000246020	P1

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89974

AN:

152004

Hom.:

28131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.800

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.552

Gnomad EAS

AF:

0.723

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.600

GnomAD3 exomes

AF:

0.544

AC:

136464

AN:

251004

Hom.:

38485

AF XY:

0.537

AC XY:

72881

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.804

Gnomad AMR exome

AF:

0.574

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.722

Gnomad SAS exome

AF:

0.527

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.525

GnomAD4 exome

AF:

0.513

AC:

749646

AN:

1460042

Hom.:

196011

Cov.:

AF XY:

0.514

AC XY:

372979

AN XY:

726336

show subpopulations

Gnomad4 AFR exome

AF:

0.809

Gnomad4 AMR exome

AF:

0.576

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.723

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.417

Gnomad4 NFE exome

AF:

0.495

Gnomad4 OTH exome

AF:

0.543

GnomAD4 genome

AF:

0.592

AC:

90075

AN:

152122

Hom.:

28176

Cov.:

AF XY:

0.591

AC XY:

43939

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.800

Gnomad4 AMR

AF:

0.577

Gnomad4 ASJ

AF:

0.552

Gnomad4 EAS

AF:

0.723

Gnomad4 SAS

AF:

0.537

Gnomad4 FIN

AF:

0.419

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.598

Alfa

AF:

0.524

Hom.:

42258

Bravo

AF:

0.616

TwinsUK

AF:

0.494

AC:

1831

ALSPAC

AF:

0.483

AC:

1863

ESP6500AA

AF:

0.786

AC:

3464

ESP6500EA

AF:

0.504

AC:

4335

ExAC

AF:

0.546

AC:

66309

Asia WGS

AF:

0.607

AC:

2108

AN:

3478

EpiCase

AF:

0.504

EpiControl

AF:

0.505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.40

DANN

Benign

0.25

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.089

T;.

MetaRNN

Benign

0.0000033

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

7.9

N;N

REVEL

Benign

0.086

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.17

MutPred

0.26

Gain of disorder (P = 0.0033);Gain of disorder (P = 0.0033);

MPC

0.093

ClinPred

0.0041

GERP RS

-0.60

Varity_R

0.068

gMVP

0.28

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