3-122341230-G-A

Position:

• chr3-122341230-G-A

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.169-209G>A 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 151,946 control chromosomes in the GnomAD database, including 1,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1526 hom., cov: 31)
• Consequence: CSTA NM_005213.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21

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=-0.99).
• BP6: Variant 3-122341230-G-A is Benign according to our data. Variant chr3-122341230-G-A is described in ClinVar as [Benign]. Clinvar id is 1268987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSTA	NM_005213.4	c.169-209G>A		intron_variant		ENST00000264474.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSTA	ENST00000264474.4	c.169-209G>A		intron_variant		1	NM_005213.4	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18708 AN: 151828 Hom.: 1528 Cov.: 31

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.0936

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.123 AC: 18699 AN: 151946 Hom.: 1526 Cov.: 31 AF XY: 0.124 AC XY: 9227 AN XY: 74294

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.0934

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.0983

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.124

Alfa AF: 0.110 Hom.: 139

Bravo AF: 0.122

Asia WGS AF: 0.217 AC: 756 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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.023
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: rs9839253; hg19: chr3-122060077;