rs12601982

Positions:

• chr17-42309656-A-G

Variant summary

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

The NM_001288718.2(STAT5A):​c.2222+172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 625,920 control chromosomes in the GnomAD database, including 13,786 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 0.20 (3413 hom., cov: 32)
  • Exomes 𝑓: 0.20 (10373 hom.)
• Consequence: STAT5A NM_001288718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT5A	NM_001288718.2	c.2222+172A>G		intron_variant		ENST00000590949.6	NP_001275647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT5A	ENST00000590949.6	c.2222+172A>G		intron_variant		1	NM_001288718.2	ENSP00000468749	P4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30687 AN: 152050 Hom.: 3406 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.198 AC: 93640 AN: 473750 Hom.: 10373 Cov.: 6 AF XY: 0.203 AC XY: 50117 AN XY: 247154

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.202 AC: 30730 AN: 152170 Hom.: 3413 Cov.: 32 AF XY: 0.204 AC XY: 15173 AN XY: 74402

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.214

Alfa AF: 0.180 Hom.: 3587

Bravo AF: 0.198

Asia WGS AF: 0.376 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.48

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: rs12601982; hg19: chr17-40461674;