chr12-57102172-C-T

Position:

• chr12-57102172-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003153.5(STAT6):​c.1512+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,146,190 control chromosomes in the GnomAD database, including 250 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 0.025 (156 hom., cov: 30)
  • Exomes 𝑓: 0.0028 (94 hom.)
• Consequence: STAT6 NM_003153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT6	NM_003153.5	c.1512+118G>A		intron_variant		ENST00000300134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT6	ENST00000300134.8	c.1512+118G>A		intron_variant		1	NM_003153.5	P1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3779 AN: 152062 Hom.: 156 Cov.: 30

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.00276 AC: 2743 AN: 994010 Hom.: 94 AF XY: 0.00244 AC XY: 1229 AN XY: 504266

Gnomad4 AFR exome AF: 0.0865

Gnomad4 AMR exome AF: 0.00544

Gnomad4 ASJ exome AF: 0.000103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000254

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000226

Gnomad4 OTH exome AF: 0.00669

GnomAD4 genome AF: 0.0249 AC: 3793 AN: 152180 Hom.: 156 Cov.: 30 AF XY: 0.0247 AC XY: 1838 AN XY: 74400

Gnomad4 AFR AF: 0.0856

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0190 Hom.: 8

Bravo AF: 0.0285

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.7
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3024967; hg19: chr12-57495955;