rs555155085

chr17-42219455-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_012448.4(STAT5B):c.690C>T(p.Ala230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,437,330 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 28)
  • Exomes 𝑓: 0.00034 (4 hom.)
• Consequence: STAT5B NM_012448.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 17-42219455-G-A is Benign according to our data. Variant chr17-42219455-G-A is described in ClinVar as [Benign]. Clinvar id is 466225.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-42219455-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.45 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00241 (349/144518) while in subpopulation AFR AF= 0.00859 (333/38766). AF 95% confidence interval is 0.00783. There are 1 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT5B	NM_012448.4	c.690C>T	p.Ala230=	synonymous_variant	7/19	ENST00000293328.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT5B	ENST00000293328.8	c.690C>T	p.Ala230=	synonymous_variant	7/19	1	NM_012448.4	P4

Frequencies

GnomAD3 genomes AF: 0.00242 AC: 349 AN: 144412 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000551

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000456

Gnomad OTH AF: 0.00259

GnomAD3 exomes AF: 0.000816 AC: 71 AN: 87048 Hom.: 1 AF XY: 0.000744 AC XY: 34 AN XY: 45716

Gnomad AFR exome AF: 0.00995

Gnomad AMR exome AF: 0.000382

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000238

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000323

Gnomad OTH exome AF: 0.000362

GnomAD4 exome AF: 0.000338 AC: 437 AN: 1292812 Hom.: 4 Cov.: 22 AF XY: 0.000279 AC XY: 178 AN XY: 636914

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.000355

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000677

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000160

Gnomad4 OTH exome AF: 0.000664

GnomAD4 genome AF: 0.00241 AC: 349 AN: 144518 Hom.: 1 Cov.: 28 AF XY: 0.00223 AC XY: 156 AN XY: 69972

Gnomad4 AFR AF: 0.00859

Gnomad4 AMR AF: 0.000550

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000456

Gnomad4 OTH AF: 0.00256

Alfa AF: 0.00147 Hom.: 0

Bravo AF: 0.00303

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 03, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	8.7
Dann	Benign	0.70

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: rs555155085; hg19: chr17-40371473;