17-42201524-GCACACACACACACACACACACACA-GCACACACACACACACACACA

Variant names:

• chr17-42201524-GCACA-G
• rs57573850
• NM_012448.4:c.*210_*213delTGTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_012448.4(STAT5B):​c.*210_*213delTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 612,544 control chromosomes in the GnomAD database, including 440 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.071 (351 hom., cov: 21)
  • Exomes 𝑓: 0.067 (89 hom.)
• Consequence: STAT5B NM_012448.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 0 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.074 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.*210_*213delTGTG		3_prime_UTR	Exon 19 of 19	NP_036580.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5B	ENST00000293328.8	TSL:1 MANE Select	c.*210_*213delTGTG		3_prime_UTR	Exon 19 of 19	ENSP00000293328.3	P51692
	STAT5B	ENST00000951702.1		c.*210_*213delTGTG		3_prime_UTR	Exon 20 of 20	ENSP00000621761.1
	STAT5B	ENST00000415845.2	TSL:4	c.*210_*213delTGTG		3_prime_UTR	Exon 19 of 19	ENSP00000398379.2	P51692

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10316 AN: 145694 Hom.: 351 Cov.: 21

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.0536

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0263

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.0514

GnomAD4 exome AF: 0.0668 AC: 31179 AN: 466760 Hom.: 89 AF XY: 0.0658 AC XY: 16189 AN XY: 246060

African (AFR) AF: 0.0817 AC: 1088 AN: 13318

American (AMR) AF: 0.0290 AC: 801 AN: 27606

Ashkenazi Jewish (ASJ) AF: 0.0315 AC: 486 AN: 15414

East Asian (EAS) AF: 0.0605 AC: 1867 AN: 30852

South Asian (SAS) AF: 0.0558 AC: 2712 AN: 48624

European-Finnish (FIN) AF: 0.115 AC: 3513 AN: 30668

Middle Eastern (MID) AF: 0.0179 AC: 37 AN: 2070

European-Non Finnish (NFE) AF: 0.0700 AC: 18995 AN: 271484

Other (OTH) AF: 0.0629 AC: 1680 AN: 26724

GnomAD4 genome AF: 0.0708 AC: 10320 AN: 145784 Hom.: 351 Cov.: 21 AF XY: 0.0702 AC XY: 4971 AN XY: 70806

African (AFR) AF: 0.0724 AC: 2911 AN: 40234

American (AMR) AF: 0.0369 AC: 532 AN: 14422

Ashkenazi Jewish (ASJ) AF: 0.0306 AC: 102 AN: 3338

East Asian (EAS) AF: 0.0378 AC: 185 AN: 4896

South Asian (SAS) AF: 0.0512 AC: 231 AN: 4514

European-Finnish (FIN) AF: 0.128 AC: 1227 AN: 9574

Middle Eastern (MID) AF: 0.0286 AC: 8 AN: 280

European-Non Finnish (NFE) AF: 0.0757 AC: 4973 AN: 65668

Other (OTH) AF: 0.0525 AC: 103 AN: 1962

Alfa AF: 0.0309 Hom.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
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: rs57573850; hg19: chr17-40353542;