chr17-42329511-G-C

Variant names:

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.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

Publications

118 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
STAT3-related early-onset multisystem autoimmune disease
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
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=-0.84).

BP6

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

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139276.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STAT3	NM_139276.3	MANE Select	c.1233+43C>G	intron	N/A	NP_644805.1	P40763-1
STAT3	NM_001369512.1		c.1233+43C>G	intron	N/A	NP_001356441.1	P40763-1
STAT3	NM_001369513.1		c.1233+43C>G	intron	N/A	NP_001356442.1	P40763-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STAT3	ENST00000264657.10	TSL:1 MANE Select	c.1233+43C>G	intron	N/A	ENSP00000264657.4	P40763-1
STAT3	ENST00000588969.5	TSL:1	c.1233+43C>G	intron	N/A	ENSP00000467985.1	P40763-1
STAT3	ENST00000404395.3	TSL:1	c.1233+43C>G	intron	N/A	ENSP00000384943.3	P40763-2

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

GnomAD2 exomes

AF:

0.588

AC:

147772

AN:

251422

AF XY:

0.593

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 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

African (AFR)

AF:

0.856

AC:

28666

AN:

33480

American (AMR)

AF:

0.439

AC:

19641

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

14601

AN:

26136

East Asian (EAS)

AF:

0.582

AC:

23107

AN:

39690

South Asian (SAS)

AF:

0.625

AC:

53869

AN:

86258

European-Finnish (FIN)

AF:

0.585

AC:

31231

AN:

53418

Middle Eastern (MID)

AF:

0.592

AC:

3415

AN:

5768

European-Non Finnish (NFE)

AF:

0.610

AC:

678344

AN:

1111960

Other (OTH)

AF:

0.611

AC:

36928

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

23800

47600

71399

95199

118999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18380

36760

55140

73520

91900

<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:

0.656

AC:

99769

AN:

152072

Hom.:

33971

Cov.:

AF XY:

0.649

AC XY:

48265

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.850

AC:

35296

AN:

41512

American (AMR)

AF:

0.507

AC:

7747

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1955

AN:

3470

East Asian (EAS)

AF:

0.549

AC:

2837

AN:

5166

South Asian (SAS)

AF:

0.629

AC:

3036

AN:

4828

European-Finnish (FIN)

AF:

0.569

AC:

6003

AN:

10546

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.600

AC:

40782

AN:

67954

Other (OTH)

AF:

0.641

AC:

1351

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1649

3297

4946

6594

8243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<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:

0.587

Hom.:

14676

Bravo

AF:

0.659

Asia WGS

AF:

0.658

AC:

2283

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hyper-IgE recurrent infection syndrome 1, autosomal dominant (1)

not specified (1)

STAT3-related early-onset multisystem autoimmune disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over