NM_139276.3:c.1233+43C>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139276.3(STAT3):c.1233+43C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,613,902 control chromosomes in the GnomAD database, including 307,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33971 hom., cov: 32)

Exomes 𝑓: 0.61 ( 273364 hom. )

Consequence

STAT3
NM_139276.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.881

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-42329511-G-C is Benign according to our data. Variant chr17-42329511-G-C is described in ClinVar as [Benign]. Clinvar id is 1233827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-42329511-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT3	NM_139276.3 link	c.1233+43C>G		intron_variant	Intron 13 of 23	ENST00000264657.10	NP_644805.1	P40763-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT3	ENST00000264657.10 link	c.1233+43C>G		intron_variant	Intron 13 of 23	1	NM_139276.3	ENSP00000264657.4		P40763-1

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99670

AN:

151952

Hom.:

33929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.850

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.548

Gnomad SAS

AF:

0.629

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.637

GnomAD3 exomes

AF:

0.588

AC:

147772

AN:

251422

Hom.:

44629

AF XY:

0.593

AC XY:

80608

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.854

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.523

Gnomad SAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.605

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.609

AC:

889802

AN:

1461830

Hom.:

273364

Cov.:

AF XY:

0.608

AC XY:

442479

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.856

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.559

Gnomad4 EAS exome

AF:

0.582

Gnomad4 SAS exome

AF:

0.625

Gnomad4 FIN exome

AF:

0.585

Gnomad4 NFE exome

AF:

0.610

Gnomad4 OTH exome

AF:

0.611

GnomAD4 genome

AF:

0.656

AC:

99769

AN:

152072

Hom.:

33971

Cov.:

AF XY:

0.649

AC XY:

48265

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.850

Gnomad4 AMR

AF:

0.507

Gnomad4 ASJ

AF:

0.563

Gnomad4 EAS

AF:

0.549

Gnomad4 SAS

AF:

0.629

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.600

Gnomad4 OTH

AF:

0.641

Alfa

AF:

0.587

Hom.:

14676

Bravo

AF:

0.659

Asia WGS

AF:

0.658

AC:

2283

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 75% of patients studied by a panel of primary immunodeficiencies. Number of patients: 72. Only high quality variants are reported. -

STAT3-related early-onset multisystem autoimmune disease

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyper-IgE recurrent infection syndrome 1, autosomal dominant

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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