17-42201524-GCACACACACACACACACACACA-GCACACACACACACACA

Variant names:

• chr17-42201524-GCACACA-G
• rs57573850
• NM_012448.4:c.*208_*213delTGTGTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_012448.4(STAT5B):​c.*208_*213delTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 615,590 control chromosomes in the GnomAD database, including 23 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.010 (22 hom., cov: 21)
  • Exomes 𝑓: 0.0025 (1 hom.)
• Consequence: STAT5B NM_012448.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1468/145816) while in subpopulation AFR AF= 0.0332 (1336/40244). AF 95% confidence interval is 0.0317. There are 22 homozygotes in gnomad4. There are 679 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5B	NM_012448.4	c.*208_*213delTGTGTG		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.*208_*213delTGTGTG		3_prime_UTR_variant	Exon 19 of 19	1	NM_012448.4	ENSP00000293328.3

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1464 AN: 145726 Hom.: 22 Cov.: 21

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00333

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00204

Gnomad SAS AF: 0.000663

Gnomad FIN AF: 0.000313

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.000731

Gnomad OTH AF: 0.00924

GnomAD4 exome AF: 0.00252 AC: 1186 AN: 469774 Hom.: 1 AF XY: 0.00238 AC XY: 590 AN XY: 247746

Gnomad4 AFR exome AF: 0.0366

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.000451

Gnomad4 EAS exome AF: 0.00103

Gnomad4 SAS exome AF: 0.00172

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00379

GnomAD4 genome AF: 0.0101 AC: 1468 AN: 145816 Hom.: 22 Cov.: 21 AF XY: 0.00959 AC XY: 679 AN XY: 70836

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00204

Gnomad4 SAS AF: 0.000664

Gnomad4 FIN AF: 0.000313

Gnomad4 NFE AF: 0.000731

Gnomad4 OTH AF: 0.00916

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;