15-68091077-T-C

Variant names:

• chr15-68091077-T-C
• rs8029670
• NM_016166.3:c.469+4327T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016166.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIAS1	NM_016166.3	MANE Select	c.469+4327T>C		intron	N/A	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.475+4327T>C		intron	N/A	NP_001307616.1	O75925-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIAS1	ENST00000249636.11	TSL:1 MANE Select	c.469+4327T>C		intron	N/A	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.469+4327T>C		intron	N/A	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.571+4327T>C		intron	N/A	ENSP00000569796.1

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

African (AFR) AF: 0.290 AC: 11980 AN: 41368

American (AMR) AF: 0.519 AC: 7897 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3468

East Asian (EAS) AF: 0.800 AC: 4138 AN: 5170

South Asian (SAS) AF: 0.640 AC: 3065 AN: 4792

European-Finnish (FIN) AF: 0.479 AC: 5028 AN: 10504

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29437 AN: 67918

Other (OTH) AF: 0.424 AC: 893 AN: 2106

Alfa AF: 0.313 Hom.: 931

Bravo AF: 0.422

Asia WGS AF: 0.671 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.67
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8029670; hg19: chr15-68383415;