rs8072785

Variant names:

• chr17-42299625-C-T
• rs8072785
• NM_001288718.2:c.551-126C>T

Variant summary

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

The NM_001288718.2(STAT5A):​c.551-126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,499,900 control chromosomes in the GnomAD database, including 13,326 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 0.18 (4022 hom., cov: 30)
  • Exomes 𝑓: 0.10 (9304 hom.)
• Consequence: STAT5A NM_001288718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5A	NM_001288718.2	c.551-126C>T		intron_variant	Intron 5 of 18	ENST00000590949.6	NP_001275647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5A	ENST00000590949.6	c.551-126C>T		intron_variant	Intron 5 of 18	1	NM_001288718.2	ENSP00000468749.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26649 AN: 152128 Hom.: 4019 Cov.: 30

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.105 AC: 140971 AN: 1347654 Hom.: 9304 AF XY: 0.103 AC XY: 68156 AN XY: 663418

African (AFR) AF: 0.413 AC: 12633 AN: 30612

American (AMR) AF: 0.0614 AC: 2021 AN: 32920

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 1381 AN: 21494

East Asian (EAS) AF: 0.000500 AC: 19 AN: 37982

South Asian (SAS) AF: 0.0740 AC: 5449 AN: 73658

European-Finnish (FIN) AF: 0.0637 AC: 2848 AN: 44738

Middle Eastern (MID) AF: 0.112 AC: 582 AN: 5204

European-Non Finnish (NFE) AF: 0.105 AC: 109766 AN: 1045302

Other (OTH) AF: 0.113 AC: 6272 AN: 55744

GnomAD4 genome AF: 0.175 AC: 26683 AN: 152246 Hom.: 4022 Cov.: 30 AF XY: 0.170 AC XY: 12670 AN XY: 74448

African (AFR) AF: 0.407 AC: 16878 AN: 41500

American (AMR) AF: 0.0942 AC: 1442 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3466

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5190

South Asian (SAS) AF: 0.0719 AC: 347 AN: 4826

European-Finnish (FIN) AF: 0.0658 AC: 699 AN: 10628

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0987 AC: 6711 AN: 68018

Other (OTH) AF: 0.152 AC: 320 AN: 2112

Alfa AF: 0.125 Hom.: 5158

Bravo AF: 0.187

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.095
DANN	Benign	0.64
PhyloP100		-3.4
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: rs8072785; hg19: chr17-40451643;