3-122341102-C-T

Position:

• chr3-122341102-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSTA	NM_005213.4	c.169-337C>T		intron_variant		ENST00000264474.4	NP_005204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSTA	ENST00000264474.4	c.169-337C>T		intron_variant		1	NM_005213.4	ENSP00000264474.3

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

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.0846

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.515

Alfa AF: 0.541 Hom.: 2807

Bravo AF: 0.497

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.55

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: rs7631500; hg19: chr3-122059949;