rs324013

Variant names:

• chr12-57116878-C-T
• rs324013
• ENST00000556155.5:c.-21-8579G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000556155.5(STAT6):​c.-21-8579G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,012 control chromosomes in the GnomAD database, including 18,832 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 0.49 (18832 hom., cov: 32)
• Consequence: STAT6 ENST00000556155.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 26 publications found

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 Gene-Disease associations (from GenCC):

• hyper-IgE syndrome 6, autosomal dominant, with recurrent infections

  Inheritance: AD Classification: STRONG Submitted by: ClinGen, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556155.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT6	ENST00000556155.5	TSL:1	c.-21-8579G>A		intron	N/A	ENSP00000451742.1	P42226-1
	STAT6	ENST00000553499.6	TSL:4	c.-21-8579G>A		intron	N/A	ENSP00000451074.2	P42226-1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74963 AN: 151894 Hom.: 18805 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.452

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.494 AC: 75041 AN: 152012 Hom.: 18832 Cov.: 32 AF XY: 0.495 AC XY: 36776 AN XY: 74326

African (AFR) AF: 0.472 AC: 19564 AN: 41438

American (AMR) AF: 0.546 AC: 8338 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3468

East Asian (EAS) AF: 0.396 AC: 2047 AN: 5172

South Asian (SAS) AF: 0.425 AC: 2047 AN: 4816

European-Finnish (FIN) AF: 0.536 AC: 5656 AN: 10554

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34594 AN: 67968

Other (OTH) AF: 0.448 AC: 947 AN: 2112

Alfa AF: 0.497 Hom.: 32251

Bravo AF: 0.492

Asia WGS AF: 0.440 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.63
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs324013;

hg19: chr12-57510661;