Variant chr17-42313892-T-C 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.*1853A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 232,250 control chromosomes in the GnomAD database, including 7,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5575 hom., cov: 32)

Exomes 𝑓: 0.23 ( 2335 hom. )

Consequence

STAT3
NM_139276.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.291

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=-0.79).

BP6

Variant 17-42313892-T-C is Benign according to our data. Variant chr17-42313892-T-C is described in ClinVar as [Benign]. Clinvar id is 323213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT3	NM_139276.3 linkuse as main transcript	c.*1853A>G		3_prime_UTR_variant	24/24	ENST00000264657.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT3	ENST00000264657.10 linkuse as main transcript	c.*1853A>G		3_prime_UTR_variant	24/24	1	NM_139276.3	A1	P40763-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38321

AN:

152016

Hom.:

5564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.232

AC:

18588

AN:

80116

Hom.:

2335

Cov.:

AF XY:

0.235

AC XY:

8665

AN XY:

36918

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.278

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.252

AC:

38369

AN:

152134

Hom.:

5575

Cov.:

AF XY:

0.253

AC XY:

18813

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.207

Hom.:

6004

Bravo

AF:

0.254

Asia WGS

AF:

0.389

AC:

1349

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hyper-IgE recurrent infection syndrome 1, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.8

DANN

Benign

0.73

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