chr15-68141874-T-TG

Variant names:

• chr15-68141874-T-TG
• rs113300929
• NM_016166.3:c.470-72_470-71insG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016166.3(PIAS1):​c.470-72_470-71insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 585,088 control chromosomes in the GnomAD database, including 19,882 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7494 hom., cov: 0)
  • Exomes 𝑓: 0.40 (12388 hom.)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 15-68141874-T-TG is Benign according to our data. Variant chr15-68141874-T-TG is described in ClinVar as Benign. ClinVar VariationId is 1279301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 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.470-72_470-71insG		intron	N/A	NP_057250.1	O75925-1
	PIAS1	NM_001320687.1		c.476-72_476-71insG		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.470-72_470-71insG		intron	N/A	ENSP00000249636.6	O75925-1
	PIAS1	ENST00000899735.1		c.470-72_470-71insG		intron	N/A	ENSP00000569794.1
	PIAS1	ENST00000899737.1		c.572-72_572-71insG		intron	N/A	ENSP00000569796.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 46117 AN: 145646 Hom.: 7489 Cov.: 0

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.00823

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.403 AC: 177069 AN: 439394 Hom.: 12388 AF XY: 0.401 AC XY: 90956 AN XY: 226958

African (AFR) AF: 0.411 AC: 4577 AN: 11132

American (AMR) AF: 0.359 AC: 5362 AN: 14950

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 5295 AN: 12506

East Asian (EAS) AF: 0.00898 AC: 81 AN: 9022

South Asian (SAS) AF: 0.294 AC: 8184 AN: 27796

European-Finnish (FIN) AF: 0.420 AC: 12222 AN: 29080

Middle Eastern (MID) AF: 0.404 AC: 1152 AN: 2848

European-Non Finnish (NFE) AF: 0.423 AC: 131289 AN: 310372

Other (OTH) AF: 0.411 AC: 8907 AN: 21688

GnomAD4 genome AF: 0.317 AC: 46126 AN: 145694 Hom.: 7494 Cov.: 0 AF XY: 0.309 AC XY: 21908 AN XY: 70924

African (AFR) AF: 0.327 AC: 13008 AN: 39812

American (AMR) AF: 0.293 AC: 4287 AN: 14612

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1123 AN: 3394

East Asian (EAS) AF: 0.00784 AC: 38 AN: 4844

South Asian (SAS) AF: 0.143 AC: 651 AN: 4550

European-Finnish (FIN) AF: 0.313 AC: 2918 AN: 9318

Middle Eastern (MID) AF: 0.410 AC: 114 AN: 278

European-Non Finnish (NFE) AF: 0.349 AC: 23033 AN: 65956

Other (OTH) AF: 0.340 AC: 692 AN: 2038

Alfa AF: 0.0610 Hom.: 48

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=22/78	disease causing (long InDel)

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: rs113300929; hg19: chr15-68434212;