12-57096045-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003153.5(STAT6):​c.*527G>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 0.389 in 154,210 control chromosomes in the GnomAD database, including 13,408 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 0.39 ( 13218 hom., cov: 32)
Exomes 𝑓: 0.41 ( 190 hom. )

Consequence

STAT6
NM_003153.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

39 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STAT6NM_003153.5 linkc.*527G>A 3_prime_UTR_variant Exon 22 of 22 ENST00000300134.8 NP_003144.3 P42226-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STAT6ENST00000300134.8 linkc.*527G>A 3_prime_UTR_variant Exon 22 of 22 1 NM_003153.5 ENSP00000300134.3 P42226-1

Frequencies

GnomAD3 genomes
AF:
0.389
AC:
59164
AN:
151930
Hom.:
13216
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.167
Gnomad AMI
AF:
0.293
Gnomad AMR
AF:
0.434
Gnomad ASJ
AF:
0.447
Gnomad EAS
AF:
0.253
Gnomad SAS
AF:
0.424
Gnomad FIN
AF:
0.499
Gnomad MID
AF:
0.417
Gnomad NFE
AF:
0.504
Gnomad OTH
AF:
0.404
GnomAD4 exome
AF:
0.415
AC:
897
AN:
2162
Hom.:
190
Cov.:
0
AF XY:
0.424
AC XY:
486
AN XY:
1146
show subpopulations
African (AFR)
AF:
0.167
AC:
14
AN:
84
American (AMR)
AF:
0.357
AC:
20
AN:
56
Ashkenazi Jewish (ASJ)
AF:
0.357
AC:
20
AN:
56
East Asian (EAS)
AF:
0.149
AC:
17
AN:
114
South Asian (SAS)
AF:
0.389
AC:
14
AN:
36
European-Finnish (FIN)
AF:
0.484
AC:
60
AN:
124
Middle Eastern (MID)
AF:
0.313
AC:
5
AN:
16
European-Non Finnish (NFE)
AF:
0.445
AC:
689
AN:
1548
Other (OTH)
AF:
0.453
AC:
58
AN:
128
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
0
28
56
85
113
141
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.389
AC:
59165
AN:
152048
Hom.:
13218
Cov.:
32
AF XY:
0.388
AC XY:
28803
AN XY:
74302
show subpopulations
African (AFR)
AF:
0.166
AC:
6891
AN:
41476
American (AMR)
AF:
0.435
AC:
6646
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.447
AC:
1548
AN:
3466
East Asian (EAS)
AF:
0.253
AC:
1305
AN:
5154
South Asian (SAS)
AF:
0.424
AC:
2043
AN:
4820
European-Finnish (FIN)
AF:
0.499
AC:
5279
AN:
10580
Middle Eastern (MID)
AF:
0.414
AC:
121
AN:
292
European-Non Finnish (NFE)
AF:
0.504
AC:
34224
AN:
67960
Other (OTH)
AF:
0.399
AC:
841
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1711
3422
5132
6843
8554
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
564
1128
1692
2256
2820
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.456
Hom.:
30208
Bravo
AF:
0.379
Asia WGS
AF:
0.331
AC:
1153
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.79
DANN
Benign
0.55
PhyloP100
-1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
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

Publications

Other links and lift over

dbSNP: rs703817; hg19: chr12-57489828; API