rs4029774

Positions:

• chr17-42276943-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000698776.1(STAT5B):​c.-11+10844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,136 control chromosomes in the GnomAD database, including 11,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11612 hom., cov: 32)
• Consequence: STAT5B ENST00000698776.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT5B	XM_024450897.2	c.-11+10844T>C		intron_variant
STAT5B	XM_047436593.1	c.-136+10844T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT5B	ENST00000698776.1	c.-11+10844T>C		intron_variant				P4
STAT5B	ENST00000698777.1	c.-11+11517T>C		intron_variant				P4

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55579 AN: 152018 Hom.: 11573 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.367

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.366 AC: 55672 AN: 152136 Hom.: 11612 Cov.: 32 AF XY: 0.362 AC XY: 26950 AN XY: 74386

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.367

Alfa AF: 0.308 Hom.: 8036

Bravo AF: 0.369

Asia WGS AF: 0.445 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4029774; hg19: chr17-40428961;