chr17-42300657-C-A

Variant names:

• chr17-42300657-C-A
• rs2293157
• NM_001288718.2:c.834-58C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288718.2(STAT5A):​c.834-58C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,612,802 control chromosomes in the GnomAD database, including 81,791 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 0.39 (14449 hom., cov: 31)
  • Exomes 𝑓: 0.29 (67342 hom.)
• Consequence: STAT5A NM_001288718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5A	NM_001288718.2	c.834-58C>A		intron_variant	Intron 7 of 18	ENST00000590949.6	NP_001275647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5A	ENST00000590949.6	c.834-58C>A		intron_variant	Intron 7 of 18	1	NM_001288718.2	ENSP00000468749.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58818 AN: 151718 Hom.: 14411 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.292 AC: 426826 AN: 1460966 Hom.: 67342 AF XY: 0.295 AC XY: 214171 AN XY: 726790

African (AFR) AF: 0.716 AC: 23950 AN: 33462

American (AMR) AF: 0.154 AC: 6864 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 8309 AN: 26126

East Asian (EAS) AF: 0.346 AC: 13718 AN: 39622

South Asian (SAS) AF: 0.395 AC: 34078 AN: 86204

European-Finnish (FIN) AF: 0.241 AC: 12886 AN: 53408

Middle Eastern (MID) AF: 0.350 AC: 1889 AN: 5390

European-Non Finnish (NFE) AF: 0.275 AC: 305780 AN: 1111748

Other (OTH) AF: 0.321 AC: 19352 AN: 60304

GnomAD4 genome AF: 0.388 AC: 58912 AN: 151836 Hom.: 14449 Cov.: 31 AF XY: 0.385 AC XY: 28571 AN XY: 74186

African (AFR) AF: 0.698 AC: 28869 AN: 41334

American (AMR) AF: 0.217 AC: 3319 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3466

East Asian (EAS) AF: 0.353 AC: 1809 AN: 5120

South Asian (SAS) AF: 0.418 AC: 2011 AN: 4806

European-Finnish (FIN) AF: 0.241 AC: 2546 AN: 10586

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18117 AN: 67930

Other (OTH) AF: 0.369 AC: 778 AN: 2108

Alfa AF: 0.143 Hom.: 224

Bravo AF: 0.397

Asia WGS AF: 0.448 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.81
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293157; hg19: chr17-40452675; COSMIC: COSV61809071; COSMIC: COSV61809071;