rs3198502

Positions:

• chr17-42310976-G-T

Variant summary

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

The NM_001288718.2(STAT5A):​c.*307G>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 0.243 in 387,336 control chromosomes in the GnomAD database, including 13,408 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 0.27 (6402 hom., cov: 32)
  • Exomes 𝑓: 0.23 (7006 hom.)
• Consequence: STAT5A NM_001288718.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

Genes affected

STAT5A (HGNC:11366): (signal transducer and activator of transcription 5A) The protein encoded by this gene is a member of the STAT family of transcription factors. 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 by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin, and different growth hormones. Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for tumorigenesis. The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT5A	NM_001288718.2	c.*307G>T		3_prime_UTR_variant	19/19	ENST00000590949.6	NP_001275647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT5A	ENST00000590949.6	c.*307G>T		3_prime_UTR_variant	19/19	1	NM_001288718.2	ENSP00000468749	P4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40391 AN: 151854 Hom.: 6388 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.228 AC: 53574 AN: 235364 Hom.: 7006 Cov.: 3 AF XY: 0.234 AC XY: 28872 AN XY: 123274

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.359

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.266 AC: 40445 AN: 151972 Hom.: 6402 Cov.: 32 AF XY: 0.267 AC XY: 19845 AN XY: 74284

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.271

Alfa AF: 0.206 Hom.: 3366

Bravo AF: 0.269

Asia WGS AF: 0.401 AC: 1389 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.79
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3198502; hg19: chr17-40462994;