chr17-42201524-GCACACACA-G

Variant names:

• chr17-42201524-GCACACACA-G
• rs57573850
• NM_012448.4:c.*206_*213delTGTGTGTG

Variant summary

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

The NM_012448.4(STAT5B):​c.*206_*213delTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 617,378 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0016 (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 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 eas. gnomad4 allele frequency = 0.000617 (90/145828) while in subpopulation EAS AF= 0.00633 (31/4896). AF 95% confidence interval is 0.00458. There are 0 homozygotes in gnomad4. There are 50 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.*206_*213delTGTGTGTG		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.*206_*213delTGTGTGTG		3_prime_UTR_variant	Exon 19 of 19	1	NM_012448.4	ENSP00000293328.3

Frequencies

GnomAD3 genomes AF: 0.000604 AC: 88 AN: 145738 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00631

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000183

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00160 AC: 756 AN: 471550 Hom.: 1 AF XY: 0.00152 AC XY: 378 AN XY: 248614

Gnomad4 AFR exome AF: 0.00151

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000644

Gnomad4 EAS exome AF: 0.0214

Gnomad4 SAS exome AF: 0.0000605

Gnomad4 FIN exome AF: 0.000130

Gnomad4 NFE exome AF: 0.000190

Gnomad4 OTH exome AF: 0.000408

GnomAD4 genome AF: 0.000617 AC: 90 AN: 145828 Hom.: 0 Cov.: 21 AF XY: 0.000706 AC XY: 50 AN XY: 70840

Gnomad4 AFR AF: 0.00114

Gnomad4 AMR AF: 0.0000693

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00633

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000183

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;