rs3830585

Positions:

chr17-42323632-G-GA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_139276.3(STAT3):c.1601-8_1601-7insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,613,038 control chromosomes in the GnomAD database, including 53,571 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 12220 hom., cov: 0)

Exomes 𝑓: 0.22 ( 41351 hom. )

Consequence

STAT3
NM_139276.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.765

Variant links:

Genes affected

STAT3 (HGNC:11364): (signal transducer and activator of transcription 3) The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. This gene also plays a role in regulating host response to viral and bacterial infections. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. [provided by RefSeq, Aug 2020]

STAT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 17-42323632-G-GA is Benign according to our data. Variant chr17-42323632-G-GA is described in ClinVar as [Benign]. Clinvar id is 165294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT3	NM_139276.3 linkuse as main transcript	c.1601-8_1601-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000264657.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT3	ENST00000264657.10 linkuse as main transcript	c.1601-8_1601-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_139276.3	A1	P40763-1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51335

AN:

151992

Hom.:

12179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.675

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.246

AC:

61687

AN:

250758

Hom.:

9911

AF XY:

0.244

AC XY:

33060

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.346

Gnomad SAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.220

AC:

320944

AN:

1460928

Hom.:

41351

Cov.:

AF XY:

0.222

AC XY:

161210

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.696

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.338

AC:

51437

AN:

152110

Hom.:

12220

Cov.:

AF XY:

0.338

AC XY:

25095

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.675

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.363

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.248

Hom.:

1394

Bravo

AF:

0.349

EpiCase

AF:

0.204

EpiControl

AF:

0.206

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 30, 2013	Benign based on high population prevalence -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 08, 2018	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

STAT3-related early-onset multisystem autoimmune disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

STAT3-related early-onset multisystem autoimmune disease;CN031130:Hyper-IgE recurrent infection syndrome 1, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 06, 2022

- -

STAT3 gain of function;CN031130:Hyper-IgE recurrent infection syndrome 1, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Hyper-IgE syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hyper-IgE recurrent infection syndrome 1, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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