rs9906933

Variant names:

• chr17-42258027-G-A
• rs9906933
• NM_012448.4:c.-11+18221C>T

Variant summary

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

The NM_012448.4(STAT5B):​c.-11+18221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,872 control chromosomes in the GnomAD database, including 10,942 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 0.36 (10942 hom., cov: 32)
• Consequence: STAT5B NM_012448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 15 publications found

Genes affected

STAT5B (HGNC:11367): (signal transducer and activator of transcription 5B) 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 mediates the signal transduction triggered by various cell ligands, such as IL2, IL4, CSF1, and different growth hormones. It has been shown to be involved in diverse biological processes, such as TCR signaling, apoptosis, adult mammary gland development, and sexual dimorphism of liver gene expression. This gene was found to fuse to retinoic acid receptor-alpha (RARA) gene in a small subset of acute promyelocytic leukemias (APLL). The dysregulation of the signaling pathways mediated by this protein may be the cause of the APLL. [provided by RefSeq, Jul 2008]

STAT5B Gene-Disease associations (from GenCC):

• growth hormone insensitivity syndrome with immune dysregulation

  Inheritance: SD Classification: DEFINITIVE Submitted by: Illumina
• growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• growth hormone insensitivity with immune dysregulation 1, autosomal recessive

  Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• growth hormone insensitivity syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012448.4. 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
	STAT5B	NM_012448.4	MANE Select	c.-11+18221C>T		intron	N/A	NP_036580.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5B	ENST00000293328.8	TSL:1 MANE Select	c.-11+18221C>T		intron	N/A	ENSP00000293328.3	P51692
	STAT5B	ENST00000468312.1	TSL:1	n.159+18221C>T		intron	N/A
	STAT5B	ENST00000951702.1		c.-11+18221C>T		intron	N/A	ENSP00000621761.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54296 AN: 151754 Hom.: 10925 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.358 AC: 54363 AN: 151872 Hom.: 10942 Cov.: 32 AF XY: 0.355 AC XY: 26326 AN XY: 74208

African (AFR) AF: 0.545 AC: 22565 AN: 41420

American (AMR) AF: 0.213 AC: 3246 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3464

East Asian (EAS) AF: 0.355 AC: 1831 AN: 5156

South Asian (SAS) AF: 0.422 AC: 2032 AN: 4812

European-Finnish (FIN) AF: 0.238 AC: 2506 AN: 10538

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19973 AN: 67918

Other (OTH) AF: 0.358 AC: 753 AN: 2106

Alfa AF: 0.314 Hom.: 1682

Bravo AF: 0.360

Asia WGS AF: 0.430 AC: 1487 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.55
DANN	Benign	0.65
PhyloP100		-0.38
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: rs9906933; hg19: chr17-40410045;