chr17-42310976-G-T

Variant names:

• chr17-42310976-G-T
• rs3198502
• ENST00000587646.2:n.2312G>T

Variant summary

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

The ENST00000587646.2(STAT5A):​n.2312G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 387,336 control chromosomes in the GnomAD database, including 13,408 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 0.27 (6402 hom., cov: 32)
  • Exomes 𝑓: 0.23 (7006 hom.)
• Consequence: STAT5A ENST00000587646.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 23 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000587646.2. 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.*307G>T		3_prime_UTR	Exon 19 of 19	NP_001275647.1
	STAT5A	NM_003152.4		c.*307G>T		3_prime_UTR	Exon 20 of 20	NP_003143.2
	STAT5A	NM_001288719.2		c.*307G>T		3_prime_UTR	Exon 18 of 18	NP_001275648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5A	ENST00000587646.2	TSL:1	n.2312G>T		non_coding_transcript_exon	Exon 6 of 6
	STAT5A	ENST00000590949.6	TSL:1 MANE Select	c.*307G>T		3_prime_UTR	Exon 19 of 19	ENSP00000468749.1
	STAT5A	ENST00000345506.8	TSL:1	c.*307G>T		3_prime_UTR	Exon 20 of 20	ENSP00000341208.4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40391 AN: 151854 Hom.: 6388 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.228 AC: 53574 AN: 235364 Hom.: 7006 Cov.: 3 AF XY: 0.234 AC XY: 28872 AN XY: 123274

African (AFR) AF: 0.436 AC: 3632 AN: 8336

American (AMR) AF: 0.138 AC: 1679 AN: 12178

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 2041 AN: 7450

East Asian (EAS) AF: 0.359 AC: 5853 AN: 16282

South Asian (SAS) AF: 0.320 AC: 8297 AN: 25894

European-Finnish (FIN) AF: 0.202 AC: 2430 AN: 12048

Middle Eastern (MID) AF: 0.250 AC: 255 AN: 1022

European-Non Finnish (NFE) AF: 0.188 AC: 26085 AN: 138556

Other (OTH) AF: 0.243 AC: 3302 AN: 13598

GnomAD4 genome AF: 0.266 AC: 40445 AN: 151972 Hom.: 6402 Cov.: 32 AF XY: 0.267 AC XY: 19845 AN XY: 74284

African (AFR) AF: 0.432 AC: 17881 AN: 41404

American (AMR) AF: 0.154 AC: 2347 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1871 AN: 5164

South Asian (SAS) AF: 0.339 AC: 1635 AN: 4822

European-Finnish (FIN) AF: 0.198 AC: 2085 AN: 10554

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12777 AN: 67970

Other (OTH) AF: 0.271 AC: 570 AN: 2106

Alfa AF: 0.213 Hom.: 4876

Bravo AF: 0.269

Asia WGS AF: 0.401 AC: 1389 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.79
DANN	Benign	0.50
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3198502; hg19: chr17-40462994;