17-42201524-GCACACACACACACACACACACA-GCACACACACACACACACACACACACA

Variant names:

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

Variant summary

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

The NM_012448.4(STAT5B):​c.*210_*213dupTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 617,200 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 0.0044 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0044 (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 amr. gnomad4 allele frequency = 0.00441 (643/145820) while in subpopulation AMR AF= 0.0068 (98/14422). AF 95% confidence interval is 0.00571. There are 0 homozygotes in gnomad4. There are 293 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.*210_*213dupTGTG		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.*210_*213dupTGTG		3_prime_UTR_variant	Exon 19 of 19	1	NM_012448.4	ENSP00000293328.3

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 641 AN: 145730 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.00240

Gnomad EAS AF: 0.00163

Gnomad SAS AF: 0.00487

Gnomad FIN AF: 0.00251

Gnomad MID AF: 0.0197

Gnomad NFE AF: 0.00489

Gnomad OTH AF: 0.00513

GnomAD4 exome AF: 0.00444 AC: 2094 AN: 471380 Hom.: 0 Cov.: 0 AF XY: 0.00451 AC XY: 1120 AN XY: 248512

Gnomad4 AFR exome AF: 0.00532

Gnomad4 AMR exome AF: 0.00428

Gnomad4 ASJ exome AF: 0.000709

Gnomad4 EAS exome AF: 0.00119

Gnomad4 SAS exome AF: 0.00553

Gnomad4 FIN exome AF: 0.00240

Gnomad4 NFE exome AF: 0.00497

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.00441 AC: 643 AN: 145820 Hom.: 0 Cov.: 21 AF XY: 0.00414 AC XY: 293 AN XY: 70834

Gnomad4 AFR AF: 0.00360

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.00240

Gnomad4 EAS AF: 0.00163

Gnomad4 SAS AF: 0.00510

Gnomad4 FIN AF: 0.00251

Gnomad4 NFE AF: 0.00489

Gnomad4 OTH AF: 0.00509

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;