NM_016166.3:c.469+16959A>G

Variant names:

• chr15-68103709-A-G
• rs10162905
• NM_016166.3:c.469+16959A>G

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+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
• Publications: 4 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=-0.9).
• 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 rank	MANE	Protein	UniProt
PIAS1	NM_016166.3	c.469+16959A>G		intron_variant	Intron 2 of 13	ENST00000249636.11	NP_057250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIAS1	ENST00000249636.11	c.469+16959A>G		intron_variant	Intron 2 of 13	1	NM_016166.3	ENSP00000249636.6
PIAS1	ENST00000545237.1	c.475+16959A>G		intron_variant	Intron 3 of 14	2		ENSP00000438574.1
PIAS1	ENST00000562190.1	n.*559+16959A>G		intron_variant	Intron 4 of 5	3		ENSP00000457698.1
PIAS1	ENST00000564915.5	n.*35+15819A>G		intron_variant	Intron 3 of 4	5		ENSP00000456721.1

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

African (AFR) AF: 0.176 AC: 7286 AN: 41512

American (AMR) AF: 0.276 AC: 4211 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1133 AN: 3472

East Asian (EAS) AF: 0.00733 AC: 38 AN: 5182

South Asian (SAS) AF: 0.136 AC: 657 AN: 4820

European-Finnish (FIN) AF: 0.307 AC: 3237 AN: 10560

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23325 AN: 67976

Other (OTH) AF: 0.306 AC: 647 AN: 2112

Alfa AF: 0.296 Hom.: 4440

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
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10162905; hg19: chr15-68396047;