Variant rs146176992 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_012448.4(STAT5B):c.247C>T(p.Leu83=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00536 in 1,613,614 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0055 ( 24 hom. )

Consequence

STAT5B
NM_012448.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.28

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 17-42227567-G-A is Benign according to our data. Variant chr17-42227567-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 282341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-42227567-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00377 (573/152158) while in subpopulation SAS AF= 0.00664 (32/4820). AF 95% confidence interval is 0.00521. There are 1 homozygotes in gnomad4. There are 260 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 24 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT5B	NM_012448.4 linkuse as main transcript	c.247C>T	p.Leu83=	synonymous_variant	3/19	ENST00000293328.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT5B	ENST00000293328.8 linkuse as main transcript	c.247C>T	p.Leu83=	synonymous_variant	3/19	1	NM_012448.4	P4

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

572

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00568

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00493

AC:

1239

AN:

251106

Hom.:

AF XY:

0.00516

AC XY:

700

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.0130

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00569

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.00631

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.00552

AC:

8072

AN:

1461456

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

4135

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00668

Gnomad4 FIN exome

AF:

0.00434

Gnomad4 NFE exome

AF:

0.00573

Gnomad4 OTH exome

AF:

0.00587

GnomAD4 genome

AF:

0.00377

AC:

573

AN:

152158

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

260

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00664

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00568

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00511

Hom.:

Bravo

AF:

0.00379

EpiCase

AF:

0.00671

EpiControl

AF:

0.00640

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 04, 2015

- -

Growth hormone insensitivity with immune dysregulation 1, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

STAT5B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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