NM_001288718.2:c.376-1215C>A

Variant names:

• chr17-42294404-C-A
• rs16967637
• NM_001288718.2:c.376-1215C>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.376-1215C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,902 control chromosomes in the GnomAD database, including 7,378 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 0.30 (7378 hom., cov: 31)
• Consequence: STAT5A NM_001288718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936
• Publications: 20 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288718.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5A	NM_001288718.2	MANE Select	c.376-1215C>A		intron	N/A	NP_001275647.1
	STAT5A	NM_003152.4		c.376-1215C>A		intron	N/A	NP_003143.2
	STAT5A	NM_001288719.2		c.286-1215C>A		intron	N/A	NP_001275648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5A	ENST00000590949.6	TSL:1 MANE Select	c.376-1215C>A		intron	N/A	ENSP00000468749.1
	STAT5A	ENST00000345506.8	TSL:1	c.376-1215C>A		intron	N/A	ENSP00000341208.4
	STAT5A	ENST00000546010.6	TSL:1	c.286-1215C>A		intron	N/A	ENSP00000443107.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46172 AN: 151784 Hom.: 7356 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.304 AC: 46239 AN: 151902 Hom.: 7378 Cov.: 31 AF XY: 0.301 AC XY: 22344 AN XY: 74230

African (AFR) AF: 0.373 AC: 15434 AN: 41402

American (AMR) AF: 0.191 AC: 2913 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3468

East Asian (EAS) AF: 0.295 AC: 1527 AN: 5168

South Asian (SAS) AF: 0.412 AC: 1978 AN: 4804

European-Finnish (FIN) AF: 0.230 AC: 2432 AN: 10578

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19836 AN: 67914

Other (OTH) AF: 0.323 AC: 680 AN: 2106

Alfa AF: 0.276 Hom.: 965

Bravo AF: 0.301

Asia WGS AF: 0.394 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.19
PhyloP100		0.94
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: rs16967637; hg19: chr17-40446422;