17-42201524-GCACACACACACACACACACACA-GCACACACACACACACACACACACACACA

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_012448.4(STAT5B):​c.*208_*213dupTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 617,396 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00032 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000494 (72/145830) while in subpopulation AFR AF= 0.00117 (47/40252). AF 95% confidence interval is 0.000901. There are 0 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000494 AC: 72 AN: 145740 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000139

Gnomad ASJ AF: 0.000300

Gnomad EAS AF: 0.000407

Gnomad SAS AF: 0.000221

Gnomad FIN AF: 0.000209

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.000244

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000316 AC: 149 AN: 471566 Hom.: 0 Cov.: 0 AF XY: 0.000294 AC XY: 73 AN XY: 248624

Gnomad4 AFR exome AF: 0.00122

Gnomad4 AMR exome AF: 0.000357

Gnomad4 ASJ exome AF: 0.000773

Gnomad4 EAS exome AF: 0.0000966

Gnomad4 SAS exome AF: 0.000161

Gnomad4 FIN exome AF: 0.000195

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.000482

GnomAD4 genome AF: 0.000494 AC: 72 AN: 145830 Hom.: 0 Cov.: 21 AF XY: 0.000551 AC XY: 39 AN XY: 70840

Gnomad4 AFR AF: 0.00117

Gnomad4 AMR AF: 0.000139

Gnomad4 ASJ AF: 0.000300

Gnomad4 EAS AF: 0.000408

Gnomad4 SAS AF: 0.000221

Gnomad4 FIN AF: 0.000209

Gnomad4 NFE AF: 0.000244

Gnomad4 OTH AF: 0.00

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;