Variant 15-68142041-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0500

Variant links:

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]

PIAS1 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 952 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIAS1	NM_016166.3 link	c.554+11G>C		intron_variant		ENST00000249636.11	NP_057250.1	O75925-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PIAS1	ENST00000249636.11 link	c.554+11G>C	intron_variant	1	NM_016166.3	ENSP00000249636.6	O75925-1
PIAS1	ENST00000545237.1 link	c.560+11G>C	intron_variant	2		ENSP00000438574.1	O75925-2
PIAS1	ENST00000562190.1 link	n.*644+11G>C	intron_variant	3		ENSP00000457698.1	H3BUL7
PIAS1	ENST00000564915.5 link	n.*120+11G>C	intron_variant	5		ENSP00000456721.1	H3BSI8

Frequencies

GnomAD3 genomes

AF:

0.00627

AC:

953

AN:

152090

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00849

AC XY:

962

AN XY:

113268

show subpopulations

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.:

Cov.:

AF XY:

0.00872

AC XY:

6135

AN XY:

703400

show subpopulations

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.:

Cov.:

AF XY:

0.00593

AC XY:

441

AN XY:

74406

show subpopulations

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.:

Bravo

AF:

0.00647

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 23, 2025

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over