17-42314228-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_139276.3(STAT3):​c.*1517G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 232,954 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 86 hom., cov: 31)
Exomes 𝑓: 0.0037 ( 8 hom. )

Consequence

STAT3
NM_139276.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.228
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 17-42314228-C-T is Benign according to our data. Variant chr17-42314228-C-T is described in ClinVar as [Benign]. Clinvar id is 323219.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STAT3NM_139276.3 linkuse as main transcriptc.*1517G>A 3_prime_UTR_variant 24/24 ENST00000264657.10 NP_644805.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STAT3ENST00000264657.10 linkuse as main transcriptc.*1517G>A 3_prime_UTR_variant 24/241 NM_139276.3 ENSP00000264657 A1P40763-1

Frequencies

GnomAD3 genomes
AF:
0.0180
AC:
2738
AN:
152138
Hom.:
86
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0634
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00478
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.0119
GnomAD4 exome
AF:
0.00374
AC:
302
AN:
80698
Hom.:
8
Cov.:
0
AF XY:
0.00344
AC XY:
128
AN XY:
37188
show subpopulations
Gnomad4 AFR exome
AF:
0.0606
Gnomad4 AMR exome
AF:
0.00811
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000808
Gnomad4 OTH exome
AF:
0.00654
GnomAD4 genome
AF:
0.0180
AC:
2736
AN:
152256
Hom.:
86
Cov.:
31
AF XY:
0.0170
AC XY:
1268
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0632
Gnomad4 AMR
AF:
0.00477
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00224
Hom.:
2
Bravo
AF:
0.0205
Asia WGS
AF:
0.00375
AC:
13
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 submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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
-0.41
CADD
Benign
9.7
DANN
Benign
0.87

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.

Other links and lift over

dbSNP: rs75454844; hg19: chr17-40466246; API