NM_012448.4:c.*204_*213dupTGTGTGTGTG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_012448.4(STAT5B):​c.*204_*213dupTGTGTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 617,406 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00043 ( 1 hom., cov: 21)
Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

STAT5B
NM_012448.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.111
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000425 (62/145832) while in subpopulation AMR AF= 0.00257 (37/14424). AF 95% confidence interval is 0.00191. There are 1 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STAT5BNM_012448.4 linkc.*204_*213dupTGTGTGTGTG 3_prime_UTR_variant Exon 19 of 19 ENST00000293328.8 NP_036580.2 P51692

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STAT5BENST00000293328 linkc.*204_*213dupTGTGTGTGTG 3_prime_UTR_variant Exon 19 of 19 1 NM_012448.4 ENSP00000293328.3 P51692

Frequencies

GnomAD3 genomes
AF:
0.000425
AC:
62
AN:
145742
Hom.:
1
Cov.:
21
show subpopulations
Gnomad AFR
AF:
0.0000747
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00257
Gnomad ASJ
AF:
0.00419
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000107
Gnomad OTH
AF:
0.000513
GnomAD4 exome
AF:
0.000316
AC:
149
AN:
471574
Hom.:
0
Cov.:
0
AF XY:
0.000322
AC XY:
80
AN XY:
248626
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000606
Gnomad4 ASJ exome
AF:
0.00432
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000403
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000117
Gnomad4 OTH exome
AF:
0.00111
GnomAD4 genome
AF:
0.000425
AC:
62
AN:
145832
Hom.:
1
Cov.:
21
AF XY:
0.000423
AC XY:
30
AN XY:
70840
show subpopulations
Gnomad4 AFR
AF:
0.0000745
Gnomad4 AMR
AF:
0.00257
Gnomad4 ASJ
AF:
0.00419
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000107
Gnomad4 OTH
AF:
0.000509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs57573850; hg19: chr17-40353542; API