17-42303828-G-T

Variant names:

• chr17-42303828-G-T
• rs9906989
• NM_001288718.2:c.1170-514G>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.1170-514G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,108 control chromosomes in the GnomAD database, including 2,490 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 0.17 (2490 hom., cov: 32)
• Consequence: STAT5A NM_001288718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5A	NM_001288718.2	c.1170-514G>T		intron_variant	Intron 9 of 18	ENST00000590949.6	NP_001275647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5A	ENST00000590949.6	c.1170-514G>T		intron_variant	Intron 9 of 18	1	NM_001288718.2	ENSP00000468749.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26113 AN: 151990 Hom.: 2489 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.172 AC: 26130 AN: 152108 Hom.: 2490 Cov.: 32 AF XY: 0.175 AC XY: 12987 AN XY: 74360

African (AFR) AF: 0.152 AC: 6317 AN: 41502

American (AMR) AF: 0.108 AC: 1655 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 930 AN: 3468

East Asian (EAS) AF: 0.350 AC: 1809 AN: 5164

South Asian (SAS) AF: 0.310 AC: 1495 AN: 4816

European-Finnish (FIN) AF: 0.181 AC: 1914 AN: 10568

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11368 AN: 67990

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.163 Hom.: 2743

Bravo AF: 0.164

Asia WGS AF: 0.358 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.92
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: rs9906989; hg19: chr17-40455846;