rs12368672

Variant names:

• chr12-57118687-C-G
• rs12368672
• ENST00000556155.5:c.-22+10286G>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+10286G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,870 control chromosomes in the GnomAD database, including 9,097 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 0.33 (9097 hom., cov: 31)
• Consequence: STAT6 ENST00000556155.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.968
• Publications: 28 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 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+10286G>C		intron	N/A	ENSP00000451742.1	P42226-1
	STAT6	ENST00000553499.6	TSL:4	c.-21-10388G>C		intron	N/A	ENSP00000451074.2	P42226-1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49876 AN: 151752 Hom.: 9090 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.329 AC: 49891 AN: 151870 Hom.: 9097 Cov.: 31 AF XY: 0.330 AC XY: 24524 AN XY: 74206

African (AFR) AF: 0.177 AC: 7313 AN: 41406

American (AMR) AF: 0.416 AC: 6359 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1403 AN: 5142

South Asian (SAS) AF: 0.347 AC: 1673 AN: 4820

European-Finnish (FIN) AF: 0.424 AC: 4462 AN: 10518

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26769 AN: 67936

Other (OTH) AF: 0.294 AC: 619 AN: 2106

Alfa AF: 0.368 Hom.: 1358

Bravo AF: 0.323

Asia WGS AF: 0.309 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.40
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12368672; hg19: chr12-57512470;