rs841718

Positions:

• chr12-57099213-G-A

Variant summary

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

The NM_003153.5(STAT6):​c.1891+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,598,900 control chromosomes in the GnomAD database, including 265,026 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 0.50 (19920 hom., cov: 30)
  • Exomes 𝑓: 0.58 (245106 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT6	NM_003153.5	c.1891+81C>T		intron_variant		ENST00000300134.8	NP_003144.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT6	ENST00000300134.8	c.1891+81C>T		intron_variant		1	NM_003153.5	ENSP00000300134	P1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75402 AN: 151744 Hom.: 19919 Cov.: 30

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.577 AC: 834784 AN: 1447038 Hom.: 245106 Cov.: 29 AF XY: 0.576 AC XY: 414343 AN XY: 719898

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.497 AC: 75420 AN: 151862 Hom.: 19920 Cov.: 30 AF XY: 0.494 AC XY: 36696 AN XY: 74224

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.528

Alfa AF: 0.575 Hom.: 33618

Bravo AF: 0.491

Asia WGS AF: 0.430 AC: 1494 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	4.3
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs841718; hg19: chr12-57492996; COSMIC: COSV55665681; COSMIC: COSV55665681;