12-57119092-C-G

Variant names:

• chr12-57119092-C-G
• rs11172106
• ENST00000556155.5:c.-22+9881G>C

Variant summary

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

The ENST00000556155.5(STAT6):​c.-22+9881G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,004 control chromosomes in the GnomAD database, including 13,963 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 0.42 (13963 hom., cov: 32)
• Consequence: STAT6 ENST00000556155.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 12 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=-0.57).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.49 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.-22+9881G>C		intron	N/A	ENSP00000451742.1	P42226-1
	STAT6	ENST00000553499.6	TSL:4	c.-21-10793G>C		intron	N/A	ENSP00000451074.2	P42226-1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64220 AN: 151886 Hom.: 13948 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.423 AC: 64270 AN: 152004 Hom.: 13963 Cov.: 32 AF XY: 0.425 AC XY: 31540 AN XY: 74296

African (AFR) AF: 0.387 AC: 16032 AN: 41442

American (AMR) AF: 0.499 AC: 7626 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1578 AN: 5154

South Asian (SAS) AF: 0.380 AC: 1827 AN: 4814

European-Finnish (FIN) AF: 0.480 AC: 5068 AN: 10558

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29839 AN: 67976

Other (OTH) AF: 0.369 AC: 781 AN: 2114

Alfa AF: 0.433 Hom.: 1769

Bravo AF: 0.423

Asia WGS AF: 0.357 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.0
DANN	Benign	0.63
PhyloP100		0.42
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: rs11172106;

hg19: chr12-57512875;