rs1135669

chr17-42307719-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001288718.2(STAT5A):c.1902C>T(p.Asp634=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,488 control chromosomes in the GnomAD database, including 29,670 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 0.19 (2916 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26754 hom.)
• Consequence: STAT5A NM_001288718.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.904 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT5A	NM_001288718.2	c.1902C>T	p.Asp634=	synonymous_variant	15/19	ENST00000590949.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT5A	ENST00000590949.6	c.1902C>T	p.Asp634=	synonymous_variant	15/19	1	NM_001288718.2	P4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28400 AN: 151922 Hom.: 2908 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.192 AC: 48228 AN: 251034 Hom.: 5341 AF XY: 0.199 AC XY: 27047 AN XY: 135688

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.0845

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.344

Gnomad SAS exome AF: 0.290

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.184 AC: 269360 AN: 1461448 Hom.: 26754 Cov.: 35 AF XY: 0.188 AC XY: 136995 AN XY: 726968

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.0908

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.187 AC: 28449 AN: 152040 Hom.: 2916 Cov.: 32 AF XY: 0.190 AC XY: 14111 AN XY: 74318

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.205

Alfa AF: 0.175 Hom.: 1776

Bravo AF: 0.181

Asia WGS AF: 0.369 AC: 1280 AN: 3478

EpiCase AF: 0.176

EpiControl AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	12
Dann	Benign	0.65

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: rs1135669; hg19: chr17-40459737; COSMIC: COSV61806332; COSMIC: COSV61806332;