chr12-57116878-C-T

Position:

• chr12-57116878-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT6	ENST00000556155.5	c.-21-8579G>A		intron_variant		1		ENSP00000451742	P1
STAT6	ENST00000553499.5	c.-21-8579G>A		intron_variant		4		ENSP00000451074

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

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.448

Alfa AF: 0.496 Hom.: 25570

Bravo AF: 0.492

Asia WGS AF: 0.440 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
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: rs324013; hg19: chr12-57510661;