rs167769

Positions:

• chr12-57109992-C-T

Variant summary

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

The NM_003153.5(STAT6):​c.-22+1137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,112 control chromosomes in the GnomAD database, including 8,337 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 0.31 (8329 hom., cov: 31)
  • Exomes 𝑓: 0.37 (8 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624

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]

STAT6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT6	NM_003153.5	c.-22+1137G>A		intron_variant		ENST00000300134.8	NP_003144.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT6	ENST00000300134.8	c.-22+1137G>A		intron_variant		1	NM_003153.5	ENSP00000300134.3

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47175 AN: 151868 Hom.: 8321 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.373 AC: 47 AN: 126 Hom.: 8 Cov.: 0 AF XY: 0.344 AC XY: 33 AN XY: 96

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.310 AC: 47185 AN: 151986 Hom.: 8329 Cov.: 31 AF XY: 0.312 AC XY: 23138 AN XY: 74278

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.281

Alfa AF: 0.366 Hom.: 15334

Bravo AF: 0.302

Asia WGS AF: 0.305 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.61

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: rs167769; hg19: chr12-57503775;