rs8074524

Positions:

• chr17-42317580-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139276.3(STAT3):​c.2102-356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 373,194 control chromosomes in the GnomAD database, including 11,276 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5193 hom., cov: 32)
  • Exomes 𝑓: 0.22 (6083 hom.)
• Consequence: STAT3 NM_139276.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT3	NM_139276.3	c.2102-356G>A		intron_variant		ENST00000264657.10	NP_644805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT3	ENST00000264657.10	c.2102-356G>A		intron_variant		1	NM_139276.3	ENSP00000264657.4

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37252 AN: 151904 Hom.: 5183 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.224 AC: 49559 AN: 221172 Hom.: 6083 Cov.: 0 AF XY: 0.232 AC XY: 27127 AN XY: 117110

Gnomad4 AFR exome AF: 0.369

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.245 AC: 37295 AN: 152022 Hom.: 5193 Cov.: 32 AF XY: 0.246 AC XY: 18292 AN XY: 74332

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.256

Alfa AF: 0.210 Hom.: 2248

Bravo AF: 0.246

Asia WGS AF: 0.389 AC: 1347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
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

Other links and lift over

dbSNP: rs8074524; hg19: chr17-40469598;