17-42331448-C-A

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.1109+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,596,526 control chromosomes in the GnomAD database, including 2,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 1383 hom., cov: 31)

Exomes 𝑓: 0.0076 ( 1238 hom. )

Consequence

STAT3
NM_139276.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0750

Publications

4 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=-0.83).

BP6

Variant 17-42331448-C-A is Benign according to our data. Variant chr17-42331448-C-A is described in ClinVar as Benign. ClinVar VariationId is 1294247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 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.1109+24G>T	intron	N/A	NP_644805.1	P40763-1
STAT3	NM_001369512.1		c.1109+24G>T	intron	N/A	NP_001356441.1	P40763-1
STAT3	NM_001369513.1		c.1109+24G>T	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.1109+24G>T	intron	N/A	ENSP00000264657.4	P40763-1
STAT3	ENST00000588969.5	TSL:1	c.1109+24G>T	intron	N/A	ENSP00000467985.1	P40763-1
STAT3	ENST00000404395.3	TSL:1	c.1109+24G>T	intron	N/A	ENSP00000384943.3	P40763-2

Frequencies

GnomAD3 genomes

AF:

0.0734

AC:

11159

AN:

151990

Hom.:

1383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.0556

GnomAD2 exomes

AF:

0.0191

AC:

4760

AN:

249668

AF XY:

0.0139

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000593

Gnomad OTH exome

AF:

0.00804

GnomAD4 exome

AF:

0.00761

AC:

10991

AN:

1444418

Hom.:

1238

Cov.:

AF XY:

0.00647

AC XY:

4653

AN XY:

719472

show subpopulations

African (AFR)

AF:

0.266

AC:

8731

AN:

32872

American (AMR)

AF:

0.0144

AC:

643

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.000253

AC:

AN:

39564

South Asian (SAS)

AF:

0.000410

AC:

AN:

85384

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.0112

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.000439

AC:

482

AN:

1097240

Other (OTH)

AF:

0.0171

AC:

1025

AN:

59794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

369

738

1106

1475

1844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.0735

AC:

11173

AN:

152108

Hom.:

1383

Cov.:

AF XY:

0.0713

AC XY:

5301

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.255

AC:

10572

AN:

41428

American (AMR)

AF:

0.0275

AC:

421

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000794

AC:

AN:

68020

Other (OTH)

AF:

0.0550

AC:

116

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

436

872

1308

1744

2180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0126

Hom.:

Bravo

AF:

0.0852

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.67

PhyloP100

-0.075

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