rs1053023

Variant names:

• chr17-42313598-T-A
• rs1053023
• NM_139276.3:c.*2147A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-42313598-T-A
• chr17-42313598-T-C
• chr17-42313598-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_139276.3(STAT3):​c.*2147A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 230,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: STAT3 NM_139276.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 57 publications found

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 Gene-Disease associations (from GenCC):

• hyper-IgE recurrent infection syndrome 1, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• STAT3-related early-onset multisystem autoimmune disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, ClinGen
• permanent neonatal diabetes mellitus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000527 (8/151660) while in subpopulation AFR AF = 0.000194 (8/41206). AF 95% confidence interval is 0.0000961. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT3	NM_139276.3	c.*2147A>T		3_prime_UTR_variant	Exon 24 of 24	ENST00000264657.10	NP_644805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT3	ENST00000264657.10	c.*2147A>T		3_prime_UTR_variant	Exon 24 of 24	1	NM_139276.3	ENSP00000264657.4

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151660 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000255 AC: 2 AN: 78462 Hom.: 0 Cov.: 0 AF XY: 0.0000552 AC XY: 2 AN XY: 36224

African (AFR) AF: 0.000543 AC: 2 AN: 3684

American (AMR) AF: 0.00 AC: 0 AN: 2398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4984

East Asian (EAS) AF: 0.00 AC: 0 AN: 11178

South Asian (SAS) AF: 0.00 AC: 0 AN: 664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 48160

Other (OTH) AF: 0.00 AC: 0 AN: 6526

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151660 Hom.: 0 Cov.: 30 AF XY: 0.0000540 AC XY: 4 AN XY: 74040

African (AFR) AF: 0.000194 AC: 8 AN: 41206

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 822

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.58
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs1053023; hg19: chr17-40465616;