chr17-42201524-GCA-G

Position:

• chr17-42201524-GCA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012448.4(STAT5B):​c.*212_*213del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 435,538 control chromosomes in the GnomAD database, including 1,507 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1480 hom., cov: 21)
  • Exomes 𝑓: 0.23 (27 hom.)
• Consequence: STAT5B NM_012448.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.22

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 -10 ACMG points.

• BP6: Variant 17-42201524-GCA-G is Benign according to our data. Variant chr17-42201524-GCA-G is described in ClinVar as [Benign]. Clinvar id is 1244365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT5B	NM_012448.4	c.*212_*213del		3_prime_UTR_variant	19/19	ENST00000293328.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT5B	ENST00000293328.8	c.*212_*213del		3_prime_UTR_variant	19/19	1	NM_012448.4	P4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15033 AN: 145088 Hom.: 1472 Cov.: 21

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0804

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.0464

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0799

GnomAD4 exome AF: 0.231 AC: 67118 AN: 290364 Hom.: 27 AF XY: 0.234 AC XY: 36034 AN XY: 154318

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.104 AC: 15077 AN: 145174 Hom.: 1480 Cov.: 21 AF XY: 0.104 AC XY: 7318 AN XY: 70482

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.0377

Gnomad4 SAS AF: 0.0623

Gnomad4 FIN AF: 0.0287

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.0793

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs57573850; hg19: chr17-40353542;