rs75130700

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_012448.4(STAT5B):c.1725C>T(p.Asp575=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

STAT5B
NM_012448.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.427

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 17-42210453-G-A is Benign according to our data. Variant chr17-42210453-G-A is described in ClinVar as [Benign]. Clinvar id is 466223.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.427 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000361 (55/152172) while in subpopulation EAS AF= 0.0054 (28/5186). AF 95% confidence interval is 0.00384. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT5B	NM_012448.4 linkuse as main transcript	c.1725C>T	p.Asp575=	synonymous_variant	14/19	ENST00000293328.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT5B	ENST00000293328.8 linkuse as main transcript	c.1725C>T	p.Asp575=	synonymous_variant	14/19	1	NM_012448.4	P4

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000608

AC:

153

AN:

251472

Hom.:

AF XY:

0.000618

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00565

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000214

AC:

313

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

162

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00418

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.000899

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000361

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00540

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.000291

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Growth hormone insensitivity with immune dysregulation 1, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

Cadd

Benign

1.9

Dann

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over