rs9817571

Positions:

• chr3-122337133-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005213.4(CSTA):​c.67-414C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,010 control chromosomes in the GnomAD database, including 1,775 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1775 hom., cov: 32)
• Consequence: CSTA NM_005213.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSTA	NM_005213.4	c.67-414C>T		intron_variant		ENST00000264474.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSTA	ENST00000264474.4	c.67-414C>T		intron_variant		1	NM_005213.4	P1
CSTA	ENST00000479204.1	c.67-414C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20556 AN: 151892 Hom.: 1777 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20548 AN: 152010 Hom.: 1775 Cov.: 32 AF XY: 0.136 AC XY: 10070 AN XY: 74290

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.141

Alfa AF: 0.144 Hom.: 889

Bravo AF: 0.134

Asia WGS AF: 0.217 AC: 754 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.8
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs9817571; hg19: chr3-122055980;