dbSNP rs8064638: STAT5B:c.-11+4011C>T (chr17-42272237-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012448.4(STAT5B):c.-11+4011C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,930 control chromosomes in the GnomAD database, including 10,815 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 0.36 ( 10815 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STAT5B
NM_012448.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.11

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:

ENSG00000236194 (HGNC:):

ENSG00000236194 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5B	NM_012448.4 link	c.-11+4011C>T		intron_variant	Intron 1 of 18	ENST00000293328.8	NP_036580.2	P51692

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5B	ENST00000293328.8 link	c.-11+4011C>T		intron_variant	Intron 1 of 18	1	NM_012448.4	ENSP00000293328.3		P51692

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54077

AN:

151812

Hom.:

10798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.355

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

Gnomad4 NFE exome

AC:

AN:

Gnomad4 Remaining exome

AC:

AN:

GnomAD4 genome

AF:

0.356

AC:

54144

AN:

151930

Hom.:

10815

Cov.:

AF XY:

0.353

AC XY:

26239

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.540

AC:

0.54017

AN:

0.54017

Gnomad4 AMR

AF:

0.212

AC:

0.21178

AN:

0.21178

Gnomad4 ASJ

AF:

0.337

AC:

0.336894

AN:

0.336894

Gnomad4 EAS

AF:

0.359

AC:

0.359049

AN:

0.359049

Gnomad4 SAS

AF:

0.423

AC:

0.422805

AN:

0.422805

Gnomad4 FIN

AF:

0.237

AC:

0.237171

AN:

0.237171

Gnomad4 NFE

AF:

0.294

AC:

0.293714

AN:

0.293714

Gnomad4 OTH

AF:

0.356

AC:

0.355651

AN:

0.355651

Heterozygous variant carriers

1651

3302

4953

6604

8255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.298

Hom.:

3723

Bravo

AF:

0.359

Asia WGS

AF:

0.436

AC:

1514

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.41

DANN

Benign

0.74

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over