Genetic Variant STAT6:c.*527G>A (chr12-57096045-C-T) – ACMG Classification: Benign (-12 pts)

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

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]

STAT6 links:

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
STAT6	NM_003153.5 link	c.*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
STAT6	ENST00000300134.8 link	c.*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.:

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.:

AF XY:

0.424

AC XY:

486

AN XY:

1146

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.357

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

AN:

East Asian (EAS)

AF:

0.149

AC:

AN:

114

South Asian (SAS)

AF:

0.389

AC:

AN:

European-Finnish (FIN)

AF:

0.484

AC:

AN:

124

Middle Eastern (MID)

AF:

0.313

AC:

AN:

European-Non Finnish (NFE)

AF:

0.445

AC:

689

AN:

1548

Other (OTH)

AF:

0.453

AC:

AN:

128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

113

141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.389

AC:

59165

AN:

152048

Hom.:

13218

Cov.:

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

1711

3422

5132

6843

8554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

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)

(source)

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

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12-57096045-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over