15-68142041-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016166.3(PIAS1):c.554+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 1,568,174 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (90 hom.)
• Consequence: PIAS1 NM_016166.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-68142041-G-C is Benign according to our data. Variant chr15-68142041-G-C is described in ClinVar as [Benign]. Clinvar id is 1640817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00625 (952/152206) while in subpopulation EAS AF= 0.0322 (167/5180). AF 95% confidence interval is 0.0282. There are 5 homozygotes in gnomad4. There are 441 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 953 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIAS1	NM_016166.3	c.554+11G>C		intron_variant		ENST00000249636.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIAS1	ENST00000249636.11	c.554+11G>C		intron_variant		1	NM_016166.3	P1
PIAS1	ENST00000545237.1	c.560+11G>C		intron_variant		2
PIAS1	ENST00000562190.1	c.*644+11G>C		intron_variant, NMD_transcript_variant		3
PIAS1	ENST00000564915.5	c.*120+11G>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 953 AN: 152090 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00782

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00798 AC: 1683 AN: 211010 Hom.: 9 AF XY: 0.00849 AC XY: 962 AN XY: 113268

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00380

Gnomad ASJ exome AF: 0.00733

Gnomad EAS exome AF: 0.0320

Gnomad SAS exome AF: 0.0103

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.00711

Gnomad OTH exome AF: 0.00635

GnomAD4 exome AF: 0.00875 AC: 12388 AN: 1415968 Hom.: 90 Cov.: 27 AF XY: 0.00872 AC XY: 6135 AN XY: 703400

Gnomad4 AFR exome AF: 0.00144

Gnomad4 AMR exome AF: 0.00369

Gnomad4 ASJ exome AF: 0.00843

Gnomad4 EAS exome AF: 0.0363

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.000923

Gnomad4 NFE exome AF: 0.00839

Gnomad4 OTH exome AF: 0.00842

GnomAD4 genome AF: 0.00625 AC: 952 AN: 152206 Hom.: 5 Cov.: 32 AF XY: 0.00593 AC XY: 441 AN XY: 74406

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00782

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00336 Hom.: 0

Bravo AF: 0.00647

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 21, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.4
Dann	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs117588299; hg19: chr15-68434379; COSMIC: COSV51030268; COSMIC: COSV51030268;