17-42201524-GCACACACACACACACACACACA-GCACACACACACACACACACACACA

Variant names:

• chr17-42201524-G-GCA
• rs57573850
• NM_012448.4:c.*212_*213dupTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_012448.4(STAT5B):​c.*212_*213dupTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 610,972 control chromosomes in the GnomAD database, including 435 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (419 hom., cov: 21)
  • Exomes 𝑓: 0.075 (16 hom.)
• Consequence: STAT5B NM_012448.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5B	NM_012448.4	c.*212_*213dupTG		3_prime_UTR_variant	Exon 19 of 19	ENST00000293328.8	NP_036580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5B	ENST00000293328	c.*212_*213dupTG		3_prime_UTR_variant	Exon 19 of 19	1	NM_012448.4	ENSP00000293328.3

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 10846 AN: 145634 Hom.: 419 Cov.: 21

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0789

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.0858

GnomAD4 exome AF: 0.0752 AC: 34975 AN: 465246 Hom.: 16 Cov.: 0 AF XY: 0.0742 AC XY: 18193 AN XY: 245192

Gnomad4 AFR exome AF: 0.0566

Gnomad4 AMR exome AF: 0.0555

Gnomad4 ASJ exome AF: 0.0690

Gnomad4 EAS exome AF: 0.0435

Gnomad4 SAS exome AF: 0.0683

Gnomad4 FIN exome AF: 0.0984

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.0800

GnomAD4 genome AF: 0.0745 AC: 10859 AN: 145726 Hom.: 419 Cov.: 21 AF XY: 0.0752 AC XY: 5321 AN XY: 70784

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.0641

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0836

Gnomad4 OTH AF: 0.0861

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57573850; hg19: chr17-40353542;