rs4029774

Variant names:

• chr17-42276943-A-G
• rs4029774
• ENST00000698776.1:c.-11+10844T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

STAT5B Gene-Disease associations (from GenCC):

• growth hormone insensitivity syndrome with immune dysregulation

  Inheritance: SD Classification: DEFINITIVE Submitted by: Illumina
• growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• growth hormone insensitivity with immune dysregulation 1, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• growth hormone insensitivity syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
STAT5B	XM_024450897.2	c.-11+10844T>C		intron_variant	Intron 1 of 18		XP_024306665.1
STAT5B	XM_047436593.1	c.-136+10844T>C		intron_variant	Intron 1 of 17		XP_047292549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5B	ENST00000698776.1	c.-11+10844T>C		intron_variant	Intron 1 of 18			ENSP00000513923.1
STAT5B	ENST00000698777.1	c.-11+11517T>C		intron_variant	Intron 1 of 18			ENSP00000513924.1
STAT5B	ENST00000415845.2	c.-326T>C		upstream_gene_variant		4		ENSP00000398379.2

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

African (AFR) AF: 0.572 AC: 23731 AN: 41500

American (AMR) AF: 0.214 AC: 3276 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1859 AN: 5154

South Asian (SAS) AF: 0.428 AC: 2066 AN: 4830

European-Finnish (FIN) AF: 0.237 AC: 2513 AN: 10604

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19993 AN: 67964

Other (OTH) AF: 0.367 AC: 776 AN: 2114

Alfa AF: 0.310 Hom.: 11433

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
PhyloP100		0.43
PromoterAI		0.026	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4029774; hg19: chr17-40428961;