NM_012448.4:c.1101C>A

Variant names:

• chr17-42218219-G-T
• rs61749920
• NM_012448.4:c.1101C>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012448.4(STAT5B):​c.1101C>A​(p.Pro367Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,614,132 control chromosomes in the GnomAD database, including 667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (39 hom., cov: 30)
  • Exomes 𝑓: 0.025 (628 hom.)
• Consequence: STAT5B NM_012448.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.22

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-42218219-G-T is Benign according to our data. Variant chr17-42218219-G-T is described in ClinVar as [Benign]. Clinvar id is 199127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-42218219-G-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-2.22 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT5B	NM_012448.4	c.1101C>A	p.Pro367Pro	synonymous_variant	Exon 9 of 19	ENST00000293328.8	NP_036580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT5B	ENST00000293328.8	c.1101C>A	p.Pro367Pro	synonymous_variant	Exon 9 of 19	1	NM_012448.4	ENSP00000293328.3

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2867 AN: 152128 Hom.: 39 Cov.: 30

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0170

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0259

GnomAD3 exomes AF: 0.0254 AC: 6348 AN: 249626 Hom.: 127 AF XY: 0.0286 AC XY: 3852 AN XY: 134874

Gnomad AFR exome AF: 0.00348

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.0529

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.0555

Gnomad FIN exome AF: 0.0177

Gnomad NFE exome AF: 0.0267

Gnomad OTH exome AF: 0.0292

GnomAD4 exome AF: 0.0252 AC: 36861 AN: 1461888 Hom.: 628 Cov.: 32 AF XY: 0.0265 AC XY: 19300 AN XY: 727246

Gnomad4 AFR exome AF: 0.00385

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.0505

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0554

Gnomad4 FIN exome AF: 0.0190

Gnomad4 NFE exome AF: 0.0241

Gnomad4 OTH exome AF: 0.0295

GnomAD4 genome AF: 0.0188 AC: 2865 AN: 152244 Hom.: 39 Cov.: 30 AF XY: 0.0187 AC XY: 1396 AN XY: 74464

Gnomad4 AFR AF: 0.00462

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0494

Gnomad4 FIN AF: 0.0170

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0220 Hom.: 16

Bravo AF: 0.0174

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Jun 23, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Apr 23, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Growth hormone insensitivity with immune dysregulation 1, autosomal recessive Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.5
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs61749920; hg19: chr17-40370237;