Variant chr3-122341427-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005213.4(CSTA):c.169-12A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 1,613,030 control chromosomes in the GnomAD database, including 3,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.084 ( 831 hom., cov: 31)

Exomes 𝑓: 0.049 ( 2265 hom. )

Consequence

CSTA
NM_005213.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003954

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

CSTA (HGNC:2481): (cystatin A) 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 kininogens. This gene encodes a stefin that functions as a cysteine protease inhibitor, forming tight complexes with papain and the cathepsins B, H, and L. The protein is one of the precursor proteins of cornified cell envelope in keratinocytes and plays a role in epidermal development and maintenance. Stefins have been proposed as prognostic and diagnostic tools for cancer. [provided by RefSeq, Jul 2008]

CSTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-122341427-A-C is Benign according to our data. Variant chr3-122341427-A-C is described in ClinVar as [Benign]. Clinvar id is 1285997.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSTA	NM_005213.4 linkuse as main transcript	c.169-12A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000264474.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSTA	ENST00000264474.4 linkuse as main transcript	c.169-12A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005213.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0837

AC:

12718

AN:

152018

Hom.:

831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0425

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.0144

Gnomad SAS

AF:

0.0468

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0655

GnomAD3 exomes

AF:

0.0553

AC:

13852

AN:

250682

Hom.:

589

AF XY:

0.0539

AC XY:

7309

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.0232

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.0160

Gnomad SAS exome

AF:

0.0511

Gnomad FIN exome

AF:

0.0846

Gnomad NFE exome

AF:

0.0516

Gnomad OTH exome

AF:

0.0485

GnomAD4 exome

AF:

0.0488

AC:

71336

AN:

1460894

Hom.:

2265

Cov.:

AF XY:

0.0487

AC XY:

35423

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.0255

Gnomad4 ASJ exome

AF:

0.0278

Gnomad4 EAS exome

AF:

0.0129

Gnomad4 SAS exome

AF:

0.0495

Gnomad4 FIN exome

AF:

0.0838

Gnomad4 NFE exome

AF:

0.0459

Gnomad4 OTH exome

AF:

0.0499

GnomAD4 genome

AF:

0.0837

AC:

12733

AN:

152136

Hom.:

831

Cov.:

AF XY:

0.0828

AC XY:

6155

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.0424

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.0145

Gnomad4 SAS

AF:

0.0464

Gnomad4 FIN

AF:

0.0853

Gnomad4 NFE

AF:

0.0474

Gnomad4 OTH

AF:

0.0653

Alfa

AF:

0.0635

Hom.:

110

Bravo

AF:

0.0847

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.39

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0

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