rs9842752

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
CSTA	NM_005213.4	c.168+368T>C		intron_variant		ENST00000264474.4	NP_005204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSTA	ENST00000264474.4	c.168+368T>C		intron_variant		1	NM_005213.4	ENSP00000264474.3
CSTA	ENST00000479204.1	c.*344T>C		3_prime_UTR_variant	2/2	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

Gnomad4 AFR exome AF: 0.0493

Gnomad4 AMR exome AF: 0.0807

Gnomad4 ASJ exome AF: 0.0851

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.0756

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.109

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

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.0968

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.123

Alfa AF: 0.117 Hom.: 264

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

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: rs9842752; hg19: chr3-122056863;