Variant 17-42307719-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.904

Variant links:

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]

STAT5A links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	c.1902C>T	p.Asp634=	synonymous_variant	15/19	1	NM_001288718.2	P4	P42229-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28400

AN:

151922

Hom.:

2908

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.188

AC XY:

136995

AN XY:

726968

show subpopulations

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.:

AF XY:

0.190

AC XY:

14111

AN XY:

74318

show subpopulations

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over