15-68146072-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016166.3(PIAS1):c.693+166C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 152,220 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.021 (113 hom., cov: 32)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198

Genes affected

PIAS1 (HGNC:2752): (protein inhibitor of activated STAT 1) This gene encodes a member of the protein inhibitor of activated STAT (PIAS) family. PIAS proteins function as SUMO E3 ligases and play important roles in many cellular processes by mediating the sumoylation of target proteins. This protein plays a central role as a transcriptional coregulator of numerous cellular pathways includign the STAT1 and nuclear factor kappaB pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-68146072-C-A is Benign according to our data. Variant chr15-68146072-C-A is described in ClinVar as [Benign]. Clinvar id is 1279140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIAS1	NM_016166.3	c.693+166C>A		intron_variant		ENST00000249636.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIAS1	ENST00000249636.11	c.693+166C>A		intron_variant		1	NM_016166.3	P1
PIAS1	ENST00000545237.1	c.699+166C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3159 AN: 152104 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00839

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0208 AC: 3167 AN: 152220 Hom.: 113 Cov.: 32 AF XY: 0.0204 AC XY: 1519 AN XY: 74438

Gnomad4 AFR AF: 0.0719

Gnomad4 AMR AF: 0.00838

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0174 Hom.: 14

Bravo AF: 0.0235

Asia WGS AF: 0.00347 AC: 12 AN: 3476

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

May 26, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	11
Dann	Benign	0.63

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: rs75775057; hg19: chr15-68438410;