rs7631500

Variant names:

• chr3-122341102-C-T
• rs7631500
• NM_005213.4:c.169-337C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005213.4(CSTA):​c.169-337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,684 control chromosomes in the GnomAD database, including 19,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (19975 hom., cov: 29)
• Consequence: CSTA NM_005213.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27
• Publications: 1 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: PanelApp Australia, Ambry Genetics, G2P, Genomics England PanelApp, 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 3-122341102-C-T is Benign according to our data. Variant chr3-122341102-C-T is described in ClinVar as Benign. ClinVar VariationId is 1283419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 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.169-337C>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.169-337C>T		intron	N/A	ENSP00000264474.3	P01040

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76153 AN: 151566 Hom.: 19966 Cov.: 29

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.502 AC: 76189 AN: 151684 Hom.: 19975 Cov.: 29 AF XY: 0.499 AC XY: 36962 AN XY: 74106

African (AFR) AF: 0.419 AC: 17322 AN: 41318

American (AMR) AF: 0.519 AC: 7921 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1855 AN: 3466

East Asian (EAS) AF: 0.0846 AC: 436 AN: 5152

South Asian (SAS) AF: 0.440 AC: 2112 AN: 4798

European-Finnish (FIN) AF: 0.545 AC: 5730 AN: 10510

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39125 AN: 67880

Other (OTH) AF: 0.515 AC: 1085 AN: 2108

Alfa AF: 0.541 Hom.: 2807

Bravo AF: 0.497

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.55
PhyloP100		-1.3
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: rs7631500; hg19: chr3-122059949;