chr17-42201524-GCACACACA-G

Variant names:

• chr17-42201524-GCACACACA-G
• rs57573850
• NM_012448.4:c.*206_*213delTGTGTGTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_012448.4(STAT5B):​c.*206_*213delTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 617,378 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0016 (1 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000617 (90/145828) while in subpopulation EAS AF = 0.00633 (31/4896). AF 95% confidence interval is 0.00458. There are 0 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.

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.*206_*213delTGTGTGTG		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.*206_*213delTGTGTGTG		3_prime_UTR	Exon 19 of 19	ENSP00000293328.3	P51692
	STAT5B	ENST00000951702.1		c.*206_*213delTGTGTGTG		3_prime_UTR	Exon 20 of 20	ENSP00000621761.1
	STAT5B	ENST00000415845.2	TSL:4	c.*206_*213delTGTGTGTG		3_prime_UTR	Exon 19 of 19	ENSP00000398379.2	P51692

Frequencies

GnomAD3 genomes AF: 0.000604 AC: 88 AN: 145738 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00631

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000183

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00160 AC: 756 AN: 471550 Hom.: 1 AF XY: 0.00152 AC XY: 378 AN XY: 248614

African (AFR) AF: 0.00151 AC: 21 AN: 13898

American (AMR) AF: 0.00 AC: 0 AN: 28030

Ashkenazi Jewish (ASJ) AF: 0.0000644 AC: 1 AN: 15526

East Asian (EAS) AF: 0.0214 AC: 664 AN: 31060

South Asian (SAS) AF: 0.0000605 AC: 3 AN: 49584

European-Finnish (FIN) AF: 0.000130 AC: 4 AN: 30836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2098

European-Non Finnish (NFE) AF: 0.000190 AC: 52 AN: 273548

Other (OTH) AF: 0.000408 AC: 11 AN: 26970

GnomAD4 genome AF: 0.000617 AC: 90 AN: 145828 Hom.: 0 Cov.: 21 AF XY: 0.000706 AC XY: 50 AN XY: 70840

African (AFR) AF: 0.00114 AC: 46 AN: 40252

American (AMR) AF: 0.0000693 AC: 1 AN: 14424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3338

East Asian (EAS) AF: 0.00633 AC: 31 AN: 4896

South Asian (SAS) AF: 0.00 AC: 0 AN: 4516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000183 AC: 12 AN: 65682

Other (OTH) AF: 0.00 AC: 0 AN: 1964

Alfa AF: 0.00 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57573850; hg19: chr17-40353542;