rs4559

chr12-57095865-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.*707G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,178 control chromosomes in the GnomAD database, including 26,921 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 0.59 (26915 hom., cov: 33)
  • Exomes 𝑓: 0.63 (6 hom.)
• Consequence: STAT6 NM_003153.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT6	NM_003153.5	c.*707G>A		3_prime_UTR_variant	22/22	ENST00000300134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT6	ENST00000300134.8	c.*707G>A		3_prime_UTR_variant	22/22	1	NM_003153.5	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89644 AN: 152036 Hom.: 26906 Cov.: 33

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.625 AC: 15 AN: 24 Hom.: 6 Cov.: 0 AF XY: 0.563 AC XY: 9 AN XY: 16

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.589 AC: 89684 AN: 152154 Hom.: 26915 Cov.: 33 AF XY: 0.582 AC XY: 43269 AN XY: 74362

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.597

Alfa AF: 0.640 Hom.: 29575

Bravo AF: 0.592

Asia WGS AF: 0.426 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.35
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs4559; hg19: chr12-57489648;