chr17-42299625-C-T

Position:

• chr17-42299625-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	Protein	UniProt
STAT5A	NM_001288718.2	c.551-126C>T		intron_variant		ENST00000590949.6	NP_001275647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT5A	ENST00000590949.6	c.551-126C>T		intron_variant		1	NM_001288718.2	ENSP00000468749	P4

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

Gnomad4 AFR exome AF: 0.413

Gnomad4 AMR exome AF: 0.0614

Gnomad4 ASJ exome AF: 0.0643

Gnomad4 EAS exome AF: 0.000500

Gnomad4 SAS exome AF: 0.0740

Gnomad4 FIN exome AF: 0.0637

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.113

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

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.0942

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0719

Gnomad4 FIN AF: 0.0658

Gnomad4 NFE AF: 0.0987

Gnomad4 OTH AF: 0.152

Alfa AF: 0.105 Hom.: 1954

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

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: rs8072785; hg19: chr17-40451643;