dbSNP rs2306581: STAT3:c.128+142G>T (chr17-42348247-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139276.3(STAT3):c.128+142G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,260,154 control chromosomes in the GnomAD database, including 101,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 20809 hom., cov: 32)

Exomes 𝑓: 0.37 ( 80486 hom. )

Consequence

STAT3
NM_139276.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.138

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=-0.85).

BP6

Variant 17-42348247-C-A is Benign according to our data. Variant chr17-42348247-C-A is described in ClinVar as [Benign]. Clinvar id is 677148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT3	NM_139276.3 link	c.128+142G>T		intron_variant	Intron 2 of 23	ENST00000264657.10	NP_644805.1	P40763-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT3	ENST00000264657.10 link	c.128+142G>T		intron_variant	Intron 2 of 23	1	NM_139276.3	ENSP00000264657.4		P40763-1

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72775

AN:

151942

Hom.:

20746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.808

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.431

GnomAD4 exome

AF:

0.371

AC:

410821

AN:

1108094

Hom.:

80486

AF XY:

0.372

AC XY:

209476

AN XY:

562764

show subpopulations

Gnomad4 AFR exome

AF:

0.828

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.370

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.451

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.392

GnomAD4 genome

AF:

0.479

AC:

72895

AN:

152060

Hom.:

20809

Cov.:

AF XY:

0.478

AC XY:

35541

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.808

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.380

Gnomad4 EAS

AF:

0.417

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.348

Gnomad4 OTH

AF:

0.438

Alfa

AF:

0.430

Hom.:

2520

Bravo

AF:

0.487

Asia WGS

AF:

0.543

AC:

1884

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.7

DANN

Benign

0.36

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