NM_012448.4:c.*210_*213delTGTG

Variant names:

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

Variant summary

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

The NM_012448.4(STAT5B):​c.*210_*213delTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 612,544 control chromosomes in the GnomAD database, including 440 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.071 (351 hom., cov: 21)
  • Exomes 𝑓: 0.067 (89 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.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5B	NM_012448.4	c.*210_*213delTGTG		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_*213delTGTG		3_prime_UTR_variant	Exon 19 of 19	1	NM_012448.4	ENSP00000293328.3

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10316 AN: 145694 Hom.: 351 Cov.: 21

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.0536

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0263

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.0514

GnomAD4 exome AF: 0.0668 AC: 31179 AN: 466760 Hom.: 89 AF XY: 0.0658 AC XY: 16189 AN XY: 246060

Gnomad4 AFR exome AF: 0.0817

Gnomad4 AMR exome AF: 0.0290

Gnomad4 ASJ exome AF: 0.0315

Gnomad4 EAS exome AF: 0.0605

Gnomad4 SAS exome AF: 0.0558

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.0700

Gnomad4 OTH exome AF: 0.0629

GnomAD4 genome AF: 0.0708 AC: 10320 AN: 145784 Hom.: 351 Cov.: 21 AF XY: 0.0702 AC XY: 4971 AN XY: 70806

Gnomad4 AFR AF: 0.0724

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.0378

Gnomad4 SAS AF: 0.0512

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0757

Gnomad4 OTH AF: 0.0525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;