rs16967611

Variant names:

• chr17-42249549-A-G
• rs16967611
• NM_012448.4:c.-10-17412T>C

Variant summary

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

The NM_012448.4(STAT5B):​c.-10-17412T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,046 control chromosomes in the GnomAD database, including 12,080 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 0.37 (12080 hom., cov: 32)
• Consequence: STAT5B NM_012448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• 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: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5B	NM_012448.4	MANE Select	c.-10-17412T>C		intron	N/A	NP_036580.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5B	ENST00000293328.8	TSL:1 MANE Select	c.-10-17412T>C		intron	N/A	ENSP00000293328.3
	STAT5B	ENST00000468312.1	TSL:1	n.160-17412T>C		intron	N/A
	STAT5B	ENST00000951702.1		c.-10-17412T>C		intron	N/A	ENSP00000621761.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56379 AN: 151928 Hom.: 12042 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.371 AC: 56470 AN: 152046 Hom.: 12080 Cov.: 32 AF XY: 0.368 AC XY: 27331 AN XY: 74350

African (AFR) AF: 0.592 AC: 24517 AN: 41432

American (AMR) AF: 0.216 AC: 3299 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1847 AN: 5178

South Asian (SAS) AF: 0.424 AC: 2047 AN: 4828

European-Finnish (FIN) AF: 0.237 AC: 2507 AN: 10576

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 20015 AN: 67978

Other (OTH) AF: 0.369 AC: 781 AN: 2114

Alfa AF: 0.341 Hom.: 1663

Bravo AF: 0.376

Asia WGS AF: 0.447 AC: 1551 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	0.48
DANN	Benign	0.80
PhyloP100		-0.89
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: rs16967611; hg19: chr17-40401567;