rs12601982

Variant names:

• chr17-42309656-A-G
• rs12601982
• ENST00000587646.2:n.992A>G

Variant summary

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

The ENST00000587646.2(STAT5A):​n.992A>G variant causes a non coding transcript exon 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 ENST00000587646.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 28 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=-0.88).
• 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 rank	MANE	Protein	UniProt
STAT5A	NM_001288718.2	c.2222+172A>G		intron_variant	Intron 18 of 18	ENST00000590949.6	NP_001275647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5A	ENST00000590949.6	c.2222+172A>G		intron_variant	Intron 18 of 18	1	NM_001288718.2	ENSP00000468749.1

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

African (AFR) AF: 0.259 AC: 3324 AN: 12842

American (AMR) AF: 0.110 AC: 2024 AN: 18406

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 3416 AN: 13606

East Asian (EAS) AF: 0.360 AC: 11050 AN: 30660

South Asian (SAS) AF: 0.288 AC: 12354 AN: 42914

European-Finnish (FIN) AF: 0.181 AC: 6297 AN: 34744

Middle Eastern (MID) AF: 0.223 AC: 523 AN: 2350

European-Non Finnish (NFE) AF: 0.169 AC: 49251 AN: 291772

Other (OTH) AF: 0.204 AC: 5401 AN: 26456

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

African (AFR) AF: 0.253 AC: 10504 AN: 41484

American (AMR) AF: 0.119 AC: 1819 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 944 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1867 AN: 5164

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4824

European-Finnish (FIN) AF: 0.181 AC: 1926 AN: 10614

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11451 AN: 68002

Other (OTH) AF: 0.214 AC: 452 AN: 2110

Alfa AF: 0.181 Hom.: 4567

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
PhyloP100		-1.7
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: rs12601982; hg19: chr17-40461674;