15-68124237-A-G

Variant names:

• chr15-68124237-A-G
• rs11071981
• NM_016166.3:c.470-17709A>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.470-17709A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,124 control chromosomes in the GnomAD database, including 4,968 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 0.21 (4968 hom., cov: 32)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIAS1	NM_016166.3	c.470-17709A>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.470-17709A>G		intron_variant	Intron 2 of 13	1	NM_016166.3	ENSP00000249636.6
PIAS1	ENST00000545237.1	c.476-17709A>G		intron_variant	Intron 3 of 14	2		ENSP00000438574.1
PIAS1	ENST00000562190.1	n.*560-17709A>G		intron_variant	Intron 4 of 5	3		ENSP00000457698.1
PIAS1	ENST00000564915.5	n.*36-17709A>G		intron_variant	Intron 3 of 4	5		ENSP00000456721.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32007 AN: 152006 Hom.: 4953 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.211 AC: 32032 AN: 152124 Hom.: 4968 Cov.: 32 AF XY: 0.218 AC XY: 16247 AN XY: 74364

African (AFR) AF: 0.0494 AC: 2053 AN: 41546

American (AMR) AF: 0.383 AC: 5844 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1063 AN: 3470

East Asian (EAS) AF: 0.666 AC: 3450 AN: 5180

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4824

European-Finnish (FIN) AF: 0.221 AC: 2329 AN: 10560

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15059 AN: 67966

Other (OTH) AF: 0.232 AC: 487 AN: 2102

Alfa AF: 0.231 Hom.: 8084

Bravo AF: 0.220

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		0.037
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: rs11071981; hg19: chr15-68416575;