NM_012448.4:c.1101C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012448.4(STAT5B):c.1101C>A(p.Pro367Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,614,132 control chromosomes in the GnomAD database, including 667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 39 hom., cov: 30)

Exomes 𝑓: 0.025 ( 628 hom. )

Consequence

STAT5B
NM_012448.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.22

Publications

10 publications found

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 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

STAT5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 17-42218219-G-T is Benign according to our data. Variant chr17-42218219-G-T is described in ClinVar as Benign. ClinVar VariationId is 199127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.22 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012448.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5B	NM_012448.4	MANE Select	c.1101C>A	p.Pro367Pro	synonymous	Exon 9 of 19	NP_036580.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STAT5B	ENST00000293328.8	TSL:1 MANE Select	c.1101C>A	p.Pro367Pro	synonymous	Exon 9 of 19	ENSP00000293328.3
STAT5B	ENST00000468312.1	TSL:1	n.1270C>A		non_coding_transcript_exon	Exon 9 of 9
STAT5B	ENST00000415845.2	TSL:4	c.1101C>A	p.Pro367Pro	synonymous	Exon 9 of 19	ENSP00000398379.2

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2867

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00463

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0256

Gnomad OTH

AF:

0.0259

GnomAD2 exomes

AF:

0.0254

AC:

6348

AN:

249626

AF XY:

0.0286

show subpopulations

Gnomad AFR exome

AF:

0.00348

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0529

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.0177

Gnomad NFE exome

AF:

0.0267

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.0252

AC:

36861

AN:

1461888

Hom.:

628

Cov.:

AF XY:

0.0265

AC XY:

19300

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00385

AC:

129

AN:

33480

American (AMR)

AF:

0.0152

AC:

678

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0505

AC:

1319

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39694

South Asian (SAS)

AF:

0.0554

AC:

4777

AN:

86258

European-Finnish (FIN)

AF:

0.0190

AC:

1017

AN:

53420

Middle Eastern (MID)

AF:

0.0562

AC:

324

AN:

5768

European-Non Finnish (NFE)

AF:

0.0241

AC:

26833

AN:

1112012

Other (OTH)

AF:

0.0295

AC:

1780

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

2575

5149

7724

10298

12873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

990

1980

2970

3960

4950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0188

AC:

2865

AN:

152244

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1396

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00462

AC:

192

AN:

41556

American (AMR)

AF:

0.0173

AC:

265

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0484

AC:

168

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.0494

AC:

238

AN:

4820

European-Finnish (FIN)

AF:

0.0170

AC:

180

AN:

10606

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0256

AC:

1741

AN:

68010

Other (OTH)

AF:

0.0256

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

139

277

416

554

693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Growth hormone insensitivity with immune dysregulation 1, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.5

(source)

DANN

Benign

0.63

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over