rs2272087

Variant names:

• chr17-42307544-A-G
• rs2272087
• NM_001288718.2:c.1775+48A>G

Variant summary

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

The NM_001288718.2(STAT5A):​c.1775+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,613,682 control chromosomes in the GnomAD database, including 30,926 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.21 (3533 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27393 hom.)
• Consequence: STAT5A NM_001288718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5A	NM_001288718.2	c.1775+48A>G		intron_variant	Intron 14 of 18	ENST00000590949.6	NP_001275647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5A	ENST00000590949.6	c.1775+48A>G		intron_variant	Intron 14 of 18	1	NM_001288718.2	ENSP00000468749.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31178 AN: 151808 Hom.: 3525 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.213

GnomAD3 exomes AF: 0.197 AC: 49390 AN: 251040 Hom.: 5582 AF XY: 0.203 AC XY: 27507 AN XY: 135710

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.0876

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.344

Gnomad SAS exome AF: 0.291

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.186 AC: 272108 AN: 1461756 Hom.: 27393 Cov.: 35 AF XY: 0.190 AC XY: 138194 AN XY: 727164

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.0944

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.206 AC: 31225 AN: 151926 Hom.: 3533 Cov.: 32 AF XY: 0.207 AC XY: 15410 AN XY: 74274

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.216

Alfa AF: 0.190 Hom.: 505

Bravo AF: 0.202

Asia WGS AF: 0.374 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.50
DANN	Benign	0.49
BranchPoint Hunter		2.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272087; hg19: chr17-40459562;