Variant 15-68141938-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_016166.3(PIAS1):c.470-8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,583,410 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

PIAS1
NM_016166.3 splice_region, intron

Scores

Splicing: ADA: 0.001053

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.187

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 15-68141938-T-G is Benign according to our data. Variant chr15-68141938-T-G is described in ClinVar as [Benign]. Clinvar id is 1657370.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 198 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIAS1	NM_016166.3 link	c.470-8T>G		splice_region_variant, intron_variant		ENST00000249636.11	NP_057250.1	O75925-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PIAS1	ENST00000249636.11 link	c.470-8T>G	splice_region_variant, intron_variant	1	NM_016166.3	ENSP00000249636.6	O75925-1
PIAS1	ENST00000545237.1 link	c.476-8T>G	splice_region_variant, intron_variant	2		ENSP00000438574.1	O75925-2
PIAS1	ENST00000562190.1 link	n.*560-8T>G	splice_region_variant, intron_variant	3		ENSP00000457698.1	H3BUL7
PIAS1	ENST00000564915.5 link	n.*36-8T>G	splice_region_variant, intron_variant	5		ENSP00000456721.1	H3BSI8

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00231

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00124

AC:

270

AN:

217472

Hom.:

AF XY:

0.00136

AC XY:

159

AN XY:

117202

show subpopulations

Gnomad AFR exome

AF:

0.000520

Gnomad AMR exome

AF:

0.000642

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000149

Gnomad FIN exome

AF:

0.000703

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.00128

GnomAD4 exome

AF:

0.00228

AC:

3268

AN:

1431160

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

1495

AN XY:

710550

show subpopulations

Gnomad4 AFR exome

AF:

0.000424

Gnomad4 AMR exome

AF:

0.000862

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000109

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.00282

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152250

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00231

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00135

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

Aug 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.050

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.43

Position offset: -24

DS_AL_spliceai

0.20

Position offset: 8

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