15-68091077-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016166.3(PIAS1):c.469+4327T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,750 control chromosomes in the GnomAD database, including 14,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14845 hom., cov: 30)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIAS1	NM_016166.3	c.469+4327T>C		intron_variant		ENST00000249636.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIAS1	ENST00000249636.11	c.469+4327T>C		intron_variant		1	NM_016166.3	P1
PIAS1	ENST00000545237.1	c.475+4327T>C		intron_variant		2
PIAS1	ENST00000562190.1	c.*559+4327T>C		intron_variant, NMD_transcript_variant		3
PIAS1	ENST00000564915.5	c.*35+3187T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64645 AN: 151632 Hom.: 14830 Cov.: 30

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.426 AC: 64686 AN: 151750 Hom.: 14845 Cov.: 30 AF XY: 0.438 AC XY: 32461 AN XY: 74146

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.424

Alfa AF: 0.315 Hom.: 901

Bravo AF: 0.422

Asia WGS AF: 0.671 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.1
Dann	Benign	0.67

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: rs8029670; hg19: chr15-68383415;