17-42242072-C-T

Variant names:

• chr17-42242072-C-T
• rs6503691
• NM_012448.4:c.-10-9935G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012448.4(STAT5B):​c.-10-9935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,872 control chromosomes in the GnomAD database, including 8,287 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 0.25 (8287 hom., cov: 31)
• Consequence: STAT5B NM_012448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 43 publications found

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: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• growth hormone insensitivity syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5B	NM_012448.4	MANE Select	c.-10-9935G>A		intron	N/A	NP_036580.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT5B	ENST00000293328.8	TSL:1 MANE Select	c.-10-9935G>A		intron	N/A	ENSP00000293328.3	P51692
	STAT5B	ENST00000468312.1	TSL:1	n.160-9935G>A		intron	N/A
	STAT5B	ENST00000951702.1		c.-10-9935G>A		intron	N/A	ENSP00000621761.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38232 AN: 151754 Hom.: 8248 Cov.: 31

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.0752

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38334 AN: 151872 Hom.: 8287 Cov.: 31 AF XY: 0.251 AC XY: 18625 AN XY: 74206

African (AFR) AF: 0.589 AC: 24364 AN: 41392

American (AMR) AF: 0.118 AC: 1793 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3462

East Asian (EAS) AF: 0.288 AC: 1489 AN: 5166

South Asian (SAS) AF: 0.281 AC: 1352 AN: 4816

European-Finnish (FIN) AF: 0.0883 AC: 930 AN: 10532

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7378 AN: 67952

Other (OTH) AF: 0.221 AC: 465 AN: 2102

Alfa AF: 0.178 Hom.: 9290

Bravo AF: 0.266

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.58
PhyloP100		1.0
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

Other links and lift over

dbSNP: rs6503691; hg19: chr17-40394090;