12-57098524-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2
The NM_003153.5(STAT6):c.2140G>A(p.Val714Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 1,614,166 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0027 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 4 hom. )
Consequence
STAT6
NM_003153.5 missense
NM_003153.5 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 0.173
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, STAT6
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005365044).
BP6
?
Variant 12-57098524-C-T is Benign according to our data. Variant chr12-57098524-C-T is described in ClinVar as [Benign]. Clinvar id is 733917.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 407 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAT6 | NM_003153.5 | c.2140G>A | p.Val714Met | missense_variant | 19/22 | ENST00000300134.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAT6 | ENST00000300134.8 | c.2140G>A | p.Val714Met | missense_variant | 19/22 | 1 | NM_003153.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00267 AC: 407AN: 152180Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.000700 AC: 176AN: 251410Hom.: 2 AF XY: 0.000508 AC XY: 69AN XY: 135878
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GnomAD4 exome AF: 0.000278 AC: 406AN: 1461868Hom.: 4 Cov.: 31 AF XY: 0.000208 AC XY: 151AN XY: 727234
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GnomAD4 genome ? AF: 0.00267 AC: 407AN: 152298Hom.: 4 Cov.: 32 AF XY: 0.00244 AC XY: 182AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;.;N;N;.;N
MutationTaster
Benign
N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;B;B;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at