chr17-42307544-A-G

Variant names:

• chr17-42307544-A-G
• rs2272087
• NM_001288718.2:c.1775+48A>G

Variant summary

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

The NM_001288718.2(STAT5A):​c.1775+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,613,682 control chromosomes in the GnomAD database, including 30,926 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.21 (3533 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27393 hom.)
• Consequence: STAT5A NM_001288718.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5A	NM_001288718.2	MANE Select	c.1775+48A>G		intron	N/A	NP_001275647.1	A0A384N5W4
	STAT5A	NM_003152.4		c.1775+48A>G		intron	N/A	NP_003143.2
	STAT5A	NM_001288719.2		c.1685+48A>G		intron	N/A	NP_001275648.1	P42229-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5A	ENST00000590949.6	TSL:1 MANE Select	c.1775+48A>G		intron	N/A	ENSP00000468749.1	P42229-1
	STAT5A	ENST00000345506.8	TSL:1	c.1775+48A>G		intron	N/A	ENSP00000341208.4	P42229-1
	STAT5A	ENST00000546010.6	TSL:1	c.1685+48A>G		intron	N/A	ENSP00000443107.1	P42229-2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31178 AN: 151808 Hom.: 3525 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.197 AC: 49390 AN: 251040 AF XY: 0.203

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.0876

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.344

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.186 AC: 272108 AN: 1461756 Hom.: 27393 Cov.: 35 AF XY: 0.190 AC XY: 138194 AN XY: 727164

African (AFR) AF: 0.275 AC: 9203 AN: 33476

American (AMR) AF: 0.0944 AC: 4219 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 6683 AN: 26136

East Asian (EAS) AF: 0.354 AC: 14032 AN: 39682

South Asian (SAS) AF: 0.292 AC: 25198 AN: 86250

European-Finnish (FIN) AF: 0.183 AC: 9768 AN: 53364

Middle Eastern (MID) AF: 0.237 AC: 1367 AN: 5766

European-Non Finnish (NFE) AF: 0.170 AC: 189250 AN: 1111974

Other (OTH) AF: 0.205 AC: 12388 AN: 60396

GnomAD4 genome AF: 0.206 AC: 31225 AN: 151926 Hom.: 3533 Cov.: 32 AF XY: 0.207 AC XY: 15410 AN XY: 74274

African (AFR) AF: 0.266 AC: 11031 AN: 41412

American (AMR) AF: 0.119 AC: 1822 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3468

East Asian (EAS) AF: 0.360 AC: 1852 AN: 5146

South Asian (SAS) AF: 0.315 AC: 1516 AN: 4808

European-Finnish (FIN) AF: 0.181 AC: 1914 AN: 10576

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11442 AN: 67952

Other (OTH) AF: 0.216 AC: 454 AN: 2098

Alfa AF: 0.191 Hom.: 528

Bravo AF: 0.202

Asia WGS AF: 0.374 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.50
DANN	Benign	0.49
PhyloP100		0.25
BranchPoint Hunter		2.0
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: rs2272087; hg19: chr17-40459562;