17-42223863-G-T

Position:

• chr17-42223863-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012448.4(STAT5B):​c.376-307C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,992 control chromosomes in the GnomAD database, including 8,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (8399 hom., cov: 31)
• Consequence: STAT5B NM_012448.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-42223863-G-T is Benign according to our data. Variant chr17-42223863-G-T is described in ClinVar as [Benign]. Clinvar id is 1220855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT5B	NM_012448.4	c.376-307C>A		intron_variant		ENST00000293328.8	NP_036580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT5B	ENST00000293328.8	c.376-307C>A		intron_variant		1	NM_012448.4	ENSP00000293328.3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42464 AN: 151872 Hom.: 8361 Cov.: 31

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.280 AC: 42561 AN: 151992 Hom.: 8399 Cov.: 31 AF XY: 0.278 AC XY: 20664 AN XY: 74294

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.229

Alfa AF: 0.168 Hom.: 4995

Bravo AF: 0.285

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs9900213; hg19: chr17-40375881;