17-42321817-G-A

Position:

• chr17-42321817-G-A

Variant summary

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

The NM_139276.3(STAT3):​c.2101+465C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,916 control chromosomes in the GnomAD database, including 5,572 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 (5572 hom., cov: 31)
• Consequence: STAT3 NM_139276.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT3	NM_139276.3	c.2101+465C>T		intron_variant		ENST00000264657.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT3	ENST00000264657.10	c.2101+465C>T		intron_variant		1	NM_139276.3	A1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38290 AN: 151796 Hom.: 5562 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38335 AN: 151916 Hom.: 5572 Cov.: 31 AF XY: 0.253 AC XY: 18804 AN XY: 74276

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.263

Alfa AF: 0.216 Hom.: 789

Bravo AF: 0.254

Asia WGS AF: 0.388 AC: 1343 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.26

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: rs9909659; hg19: chr17-40473835;