rs2306581

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139276.3(STAT3):c.128+142G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,260,154 control chromosomes in the GnomAD database, including 101,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 20809 hom., cov: 32)

Exomes 𝑓: 0.37 ( 80486 hom. )

Consequence

STAT3
NM_139276.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.138

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

hyper-IgE recurrent infection syndrome 1, autosomal dominant
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
STAT3-related early-onset multisystem autoimmune disease
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, ClinGen
permanent neonatal diabetes mellitus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

STAT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-42348247-C-A is Benign according to our data. Variant chr17-42348247-C-A is described in ClinVar as Benign. ClinVar VariationId is 677148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT3	NM_139276.3 link	c.128+142G>T		intron_variant	Intron 2 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.128+142G>T		intron_variant	Intron 2 of 23	1	NM_139276.3	ENSP00000264657.4		P40763-1

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72775

AN:

151942

Hom.:

20746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.808

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.431

GnomAD4 exome

AF:

0.371

AC:

410821

AN:

1108094

Hom.:

80486

AF XY:

0.372

AC XY:

209476

AN XY:

562764

show subpopulations

African (AFR)

AF:

0.828

AC:

22033

AN:

26596

American (AMR)

AF:

0.233

AC:

9495

AN:

40738

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

8417

AN:

22760

East Asian (EAS)

AF:

0.417

AC:

15626

AN:

37494

South Asian (SAS)

AF:

0.451

AC:

34403

AN:

76248

European-Finnish (FIN)

AF:

0.381

AC:

15541

AN:

40764

Middle Eastern (MID)

AF:

0.348

AC:

1225

AN:

3520

European-Non Finnish (NFE)

AF:

0.351

AC:

285090

AN:

811560

Other (OTH)

AF:

0.392

AC:

18991

AN:

48414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12478

24956

37434

49912

62390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8284

16568

24852

33136

41420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.479

AC:

72895

AN:

152060

Hom.:

20809

Cov.:

AF XY:

0.478

AC XY:

35541

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.808

AC:

33523

AN:

41480

American (AMR)

AF:

0.298

AC:

4546

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1317

AN:

3470

East Asian (EAS)

AF:

0.417

AC:

2153

AN:

5166

South Asian (SAS)

AF:

0.468

AC:

2252

AN:

4812

European-Finnish (FIN)

AF:

0.385

AC:

4066

AN:

10572

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23655

AN:

67982

Other (OTH)

AF:

0.438

AC:

923

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1648

3297

4945

6594

8242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.430

Hom.:

2520

Bravo

AF:

0.487

Asia WGS

AF:

0.543

AC:

1884

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.7

(source)

DANN

Benign

0.36

PhyloP100

0.14

PromoterAI

-0.0024

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over