chr17-42204342-T-G

Position:

• chr17-42204342-T-G

Variant summary

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

The NM_012448.4(STAT5B):​c.2078-1534A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 152,222 control chromosomes in the GnomAD database, including 237 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 0.047 (237 hom., cov: 32)
• Consequence: STAT5B NM_012448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT5B	NM_012448.4	c.2078-1534A>C		intron_variant		ENST00000293328.8	NP_036580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT5B	ENST00000293328.8	c.2078-1534A>C		intron_variant		1	NM_012448.4	ENSP00000293328.3

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7168 AN: 152104 Hom.: 237 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0410

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0446

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

GnomAD4 genome AF: 0.0471 AC: 7167 AN: 152222 Hom.: 237 Cov.: 32 AF XY: 0.0477 AC XY: 3547 AN XY: 74418

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0988

Gnomad4 NFE AF: 0.0636

Gnomad4 OTH AF: 0.0432

Alfa AF: 0.0570 Hom.: 395

Bravo AF: 0.0412

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.59

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: rs17500235; hg19: chr17-40356360;