12-57119092-C-G

Position:

• chr12-57119092-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.57119092C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT6	ENST00000556155.5	c.-22+9881G>C		intron_variant		1		ENSP00000451742.1
STAT6	ENST00000553499.5	c.-21-10793G>C		intron_variant		4		ENSP00000451074.2

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

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.369

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.0
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11172106; hg19: chr12-57512875;