Variant chr17-42331448-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

STAT3 (HGNC:):

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=-0.83).

BP6

Variant 17-42331448-C-A is Benign according to our data. Variant chr17-42331448-C-A is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT3	NM_139276.3 linkuse as main transcript	c.1109+24G>T		intron_variant		ENST00000264657.10	NP_644805.1	P40763-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT3	ENST00000264657.10 linkuse as main transcript	c.1109+24G>T		intron_variant		1	NM_139276.3	ENSP00000264657.4		P40763-1

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

GnomAD3 exomes

AF:

0.0191

AC:

4760

AN:

249668

Hom.:

529

AF XY:

0.0139

AC XY:

1873

AN XY:

134892

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 SAS exome

AF:

0.000299

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

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000253

Gnomad4 SAS exome

AF:

0.000410

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000439

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0735

AC:

11173

AN:

152108

Hom.:

1383

Cov.:

AF XY:

0.0713

AC XY:

5301

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.0275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.0550

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.0852

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

DANN

Benign

0.67

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