rs10162905

Positions:

• chr15-68103709-A-G

Variant summary

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

The NM_016166.3(PIAS1):​c.469+16959A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,114 control chromosomes in the GnomAD database, including 6,189 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 0.27 (6189 hom., cov: 32)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIAS1	NM_016166.3	c.469+16959A>G		intron_variant		ENST00000249636.11	NP_057250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIAS1	ENST00000249636.11	c.469+16959A>G		intron_variant		1	NM_016166.3	ENSP00000249636	P1
PIAS1	ENST00000545237.1	c.475+16959A>G		intron_variant		2		ENSP00000438574
PIAS1	ENST00000562190.1	c.*559+16959A>G		intron_variant, NMD_transcript_variant		3		ENSP00000457698
PIAS1	ENST00000564915.5	c.*35+15819A>G		intron_variant, NMD_transcript_variant		5		ENSP00000456721

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40906 AN: 151996 Hom.: 6193 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.269 AC: 40905 AN: 152114 Hom.: 6189 Cov.: 32 AF XY: 0.263 AC XY: 19566 AN XY: 74322

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.00733

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.306

Alfa AF: 0.298 Hom.: 2690

Bravo AF: 0.265

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10162905; hg19: chr15-68396047;