rs9817571

Variant names:

• chr3-122337133-C-T
• rs9817571
• NM_005213.4:c.67-414C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• peeling skin syndrome 4

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• acral peeling skin syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• exfoliative ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005213.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTA	NM_005213.4	MANE Select	c.67-414C>T		intron	N/A	NP_005204.1	P01040

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTA	ENST00000264474.4	TSL:1 MANE Select	c.67-414C>T		intron	N/A	ENSP00000264474.3	P01040
	CSTA	ENST00000479204.1	TSL:2	c.67-414C>T		intron	N/A	ENSP00000418891.1	C9J0E4

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

African (AFR) AF: 0.0717 AC: 2976 AN: 41478

American (AMR) AF: 0.109 AC: 1662 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2268 AN: 5170

South Asian (SAS) AF: 0.100 AC: 483 AN: 4820

European-Finnish (FIN) AF: 0.140 AC: 1470 AN: 10526

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10577 AN: 67962

Other (OTH) AF: 0.141 AC: 297 AN: 2108

Alfa AF: 0.143 Hom.: 1202

Bravo AF: 0.134

Asia WGS AF: 0.217 AC: 754 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.8
DANN	Benign	0.48
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9817571; hg19: chr3-122055980;