rs1059513

Positions:

• chr12-57095926-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003153.5(STAT6):​c.*646A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 152,468 control chromosomes in the GnomAD database, including 575 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 0.080 (574 hom., cov: 33)
  • Exomes 𝑓: 0.082 (1 hom.)
• Consequence: STAT6 NM_003153.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

Genes affected

STAT6 (HGNC:11368): (signal transducer and activator of transcription 6) 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 plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2) cells, expression of cell surface markers, and class switch of immunoglobulins. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT6	NM_003153.5	c.*646A>G		3_prime_UTR_variant	22/22	ENST00000300134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT6	ENST00000300134.8	c.*646A>G		3_prime_UTR_variant	22/22	1	NM_003153.5	P1

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12231 AN: 152168 Hom.: 573 Cov.: 33

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0824 AC: 15 AN: 182 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 10 AN XY: 100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0896

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0803 AC: 12231 AN: 152286 Hom.: 574 Cov.: 33 AF XY: 0.0784 AC XY: 5840 AN XY: 74472

Gnomad4 AFR AF: 0.0459

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.0837

Gnomad4 SAS AF: 0.0495

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.103

Alfa AF: 0.104 Hom.: 1948

Bravo AF: 0.0835

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.3
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1059513; hg19: chr12-57489709;