rs1135669

Variant names:

• chr17-42307719-C-T
• rs1135669
• NM_001288718.2:c.1902C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001288718.2(STAT5A):​c.1902C>T​(p.Asp634Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,488 control chromosomes in the GnomAD database, including 29,670 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 0.19 (2916 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26754 hom.)
• Consequence: STAT5A NM_001288718.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904
• Publications: 19 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.904 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 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.1902C>T	p.Asp634Asp	synonymous	Exon 15 of 19	NP_001275647.1	A0A384N5W4
	STAT5A	NM_003152.4		c.1902C>T	p.Asp634Asp	synonymous	Exon 16 of 20	NP_003143.2
	STAT5A	NM_001288719.2		c.1812C>T	p.Asp604Asp	synonymous	Exon 14 of 18	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.1902C>T	p.Asp634Asp	synonymous	Exon 15 of 19	ENSP00000468749.1	P42229-1
	STAT5A	ENST00000345506.8	TSL:1	c.1902C>T	p.Asp634Asp	synonymous	Exon 16 of 20	ENSP00000341208.4	P42229-1
	STAT5A	ENST00000546010.6	TSL:1	c.1812C>T	p.Asp604Asp	synonymous	Exon 14 of 18	ENSP00000443107.1	P42229-2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28400 AN: 151922 Hom.: 2908 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.202

GnomAD2 exomes AF: 0.192 AC: 48228 AN: 251034 AF XY: 0.199

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.0845

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: 0.190

GnomAD4 exome AF: 0.184 AC: 269360 AN: 1461448 Hom.: 26754 Cov.: 35 AF XY: 0.188 AC XY: 136995 AN XY: 726968

African (AFR) AF: 0.210 AC: 7035 AN: 33478

American (AMR) AF: 0.0908 AC: 4058 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 6680 AN: 26112

East Asian (EAS) AF: 0.353 AC: 14024 AN: 39678

South Asian (SAS) AF: 0.292 AC: 25181 AN: 86230

European-Finnish (FIN) AF: 0.183 AC: 9778 AN: 53396

Middle Eastern (MID) AF: 0.236 AC: 1359 AN: 5764

European-Non Finnish (NFE) AF: 0.170 AC: 189122 AN: 1111712

Other (OTH) AF: 0.201 AC: 12123 AN: 60374

GnomAD4 genome AF: 0.187 AC: 28449 AN: 152040 Hom.: 2916 Cov.: 32 AF XY: 0.190 AC XY: 14111 AN XY: 74318

African (AFR) AF: 0.202 AC: 8365 AN: 41452

American (AMR) AF: 0.114 AC: 1747 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1850 AN: 5166

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

European-Finnish (FIN) AF: 0.181 AC: 1920 AN: 10594

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

European-Non Finnish (NFE) AF: 0.168 AC: 11423 AN: 67960

Other (OTH) AF: 0.205 AC: 433 AN: 2114

Alfa AF: 0.179 Hom.: 2512

Bravo AF: 0.181

Asia WGS AF: 0.369 AC: 1280 AN: 3478

EpiCase AF: 0.176

EpiControl AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		0.90
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: rs1135669; hg19: chr17-40459737; COSMIC: COSV61806332; COSMIC: COSV61806332;