rs9842752

Variant names:

• chr3-122338016-T-C
• rs9842752
• NM_005213.4:c.168+368T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-122338016-T-C
• chr3-122338016-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005213.4(CSTA):​c.168+368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 197,050 control chromosomes in the GnomAD database, including 2,060 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 0.12 (1529 hom., cov: 32)
  • Exomes 𝑓: 0.12 (531 hom.)
• Consequence: CSTA NM_005213.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• 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: Genomics England PanelApp, Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.97).
• 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 rank	MANE	Protein	UniProt
CSTA	NM_005213.4	c.168+368T>C		intron_variant	Intron 2 of 2	ENST00000264474.4	NP_005204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTA	ENST00000264474.4	c.168+368T>C		intron_variant	Intron 2 of 2	1	NM_005213.4	ENSP00000264474.3
CSTA	ENST00000479204.1	c.*344T>C		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000418891.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18785 AN: 152136 Hom.: 1532 Cov.: 32

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.123 AC: 5527 AN: 44796 Hom.: 531 Cov.: 0 AF XY: 0.120 AC XY: 2834 AN XY: 23670

African (AFR) AF: 0.0493 AC: 49 AN: 994

American (AMR) AF: 0.0807 AC: 185 AN: 2292

Ashkenazi Jewish (ASJ) AF: 0.0851 AC: 107 AN: 1258

East Asian (EAS) AF: 0.404 AC: 736 AN: 1820

South Asian (SAS) AF: 0.0756 AC: 492 AN: 6510

European-Finnish (FIN) AF: 0.116 AC: 248 AN: 2132

Middle Eastern (MID) AF: 0.0647 AC: 11 AN: 170

European-Non Finnish (NFE) AF: 0.126 AC: 3420 AN: 27066

Other (OTH) AF: 0.109 AC: 279 AN: 2554

GnomAD4 genome AF: 0.123 AC: 18782 AN: 152254 Hom.: 1529 Cov.: 32 AF XY: 0.124 AC XY: 9264 AN XY: 74432

African (AFR) AF: 0.0701 AC: 2915 AN: 41554

American (AMR) AF: 0.0936 AC: 1431 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2272 AN: 5174

South Asian (SAS) AF: 0.0968 AC: 466 AN: 4816

European-Finnish (FIN) AF: 0.130 AC: 1382 AN: 10610

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.138 AC: 9387 AN: 68024

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.116 Hom.: 267

Bravo AF: 0.123

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.47
PhyloP100		-3.1
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: rs9842752; hg19: chr3-122056863;