dbSNP rs841718: STAT6:c.1891+81C>T (chr12-57099213-G-A) – 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.1891+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,598,900 control chromosomes in the GnomAD database, including 265,026 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 0.50 ( 19920 hom., cov: 30)

Exomes 𝑓: 0.58 ( 245106 hom. )

Consequence

STAT6
NM_003153.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.167

Publications

59 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT6	NM_003153.5 link	c.1891+81C>T		intron_variant	Intron 16 of 21	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.1891+81C>T		intron_variant	Intron 16 of 21	1	NM_003153.5	ENSP00000300134.3		P42226-1

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75402

AN:

151744

Hom.:

19919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.532

GnomAD4 exome

AF:

0.577

AC:

834784

AN:

1447038

Hom.:

245106

Cov.:

AF XY:

0.576

AC XY:

414343

AN XY:

719898

show subpopulations

African (AFR)

AF:

0.312

AC:

10332

AN:

33164

American (AMR)

AF:

0.537

AC:

23954

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

14119

AN:

25978

East Asian (EAS)

AF:

0.271

AC:

10733

AN:

39554

South Asian (SAS)

AF:

0.511

AC:

43882

AN:

85822

European-Finnish (FIN)

AF:

0.559

AC:

29362

AN:

52538

Middle Eastern (MID)

AF:

0.536

AC:

2999

AN:

5594

European-Non Finnish (NFE)

AF:

0.605

AC:

665508

AN:

1099856

Other (OTH)

AF:

0.566

AC:

33895

AN:

59904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

19287

38574

57860

77147

96434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17866

35732

53598

71464

89330

<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:

0.497

AC:

75420

AN:

151862

Hom.:

19920

Cov.:

AF XY:

0.494

AC XY:

36696

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.319

AC:

13211

AN:

41366

American (AMR)

AF:

0.530

AC:

8079

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

1848

AN:

3464

East Asian (EAS)

AF:

0.329

AC:

1697

AN:

5162

South Asian (SAS)

AF:

0.510

AC:

2457

AN:

4814

European-Finnish (FIN)

AF:

0.546

AC:

5763

AN:

10562

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.600

AC:

40739

AN:

67942

Other (OTH)

AF:

0.528

AC:

1111

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1829

3658

5488

7317

9146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.566

Hom.:

81918

Bravo

AF:

0.491

Asia WGS

AF:

0.430

AC:

1494

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.3

(source)

DANN

Benign

0.78

PhyloP100

-0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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