rs324015

Variant names:

• chr12-57096317-T-C
• rs324015
• NM_003153.5:c.*255A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003153.5(STAT6):​c.*255A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 464,214 control chromosomes in the GnomAD database, including 127,211 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 0.76 (43864 hom., cov: 33)
  • Exomes 𝑓: 0.72 (83347 hom.)
• Consequence: STAT6 NM_003153.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 102 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT6	NM_003153.5	c.*255A>G		3_prime_UTR_variant	Exon 22 of 22	ENST00000300134.8	NP_003144.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT6	ENST00000300134.8	c.*255A>G		3_prime_UTR_variant	Exon 22 of 22	1	NM_003153.5	ENSP00000300134.3

Frequencies

GnomAD3 genomes AF: 0.756 AC: 115032 AN: 152092 Hom.: 43818 Cov.: 33

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.724 AC: 225752 AN: 312004 Hom.: 83347 Cov.: 3 AF XY: 0.721 AC XY: 116798 AN XY: 162004

African (AFR) AF: 0.804 AC: 6430 AN: 7996

American (AMR) AF: 0.736 AC: 7069 AN: 9600

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 7848 AN: 10258

East Asian (EAS) AF: 0.400 AC: 8365 AN: 20932

South Asian (SAS) AF: 0.660 AC: 17207 AN: 26056

European-Finnish (FIN) AF: 0.721 AC: 16398 AN: 22754

Middle Eastern (MID) AF: 0.752 AC: 1138 AN: 1514

European-Non Finnish (NFE) AF: 0.758 AC: 146787 AN: 193572

Other (OTH) AF: 0.751 AC: 14510 AN: 19322

GnomAD4 genome AF: 0.756 AC: 115136 AN: 152210 Hom.: 43864 Cov.: 33 AF XY: 0.752 AC XY: 55912 AN XY: 74388

African (AFR) AF: 0.806 AC: 33490 AN: 41538

American (AMR) AF: 0.762 AC: 11672 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2633 AN: 3470

East Asian (EAS) AF: 0.533 AC: 2752 AN: 5162

South Asian (SAS) AF: 0.656 AC: 3166 AN: 4828

European-Finnish (FIN) AF: 0.709 AC: 7507 AN: 10586

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51595 AN: 68004

Other (OTH) AF: 0.759 AC: 1603 AN: 2112

Alfa AF: 0.759 Hom.: 91134

Bravo AF: 0.763

Asia WGS AF: 0.631 AC: 2195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.56
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs324015; hg19: chr12-57490100;