15-68141874-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016166.3(PIAS1):c.470-72_470-71insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 585,088 control chromosomes in the GnomAD database, including 19,882 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7494 hom., cov: 0)
  • Exomes 𝑓: 0.40 (12388 hom.)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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 -10 ACMG points.

• BP6: Variant 15-68141874-T-TG is Benign according to our data. Variant chr15-68141874-T-TG is described in ClinVar as [Benign]. Clinvar id is 1279301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIAS1	NM_016166.3	c.470-72_470-71insG		intron_variant		ENST00000249636.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIAS1	ENST00000249636.11	c.470-72_470-71insG		intron_variant		1	NM_016166.3	P1
PIAS1	ENST00000545237.1	c.476-72_476-71insG		intron_variant		2
PIAS1	ENST00000562190.1	c.*560-72_*560-71insG		intron_variant, NMD_transcript_variant		3
PIAS1	ENST00000564915.5	c.*36-72_*36-71insG		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.317 AC: 46117 AN: 145646 Hom.: 7489 Cov.: 0

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.00823

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.403 AC: 177069 AN: 439394 Hom.: 12388 AF XY: 0.401 AC XY: 90956 AN XY: 226958

Gnomad4 AFR exome AF: 0.411

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.00898

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.317 AC: 46126 AN: 145694 Hom.: 7494 Cov.: 0 AF XY: 0.309 AC XY: 21908 AN XY: 70924

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.00784

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.340

Alfa AF: 0.0610 Hom.: 48

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 14, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs113300929; hg19: chr15-68434212;