dbSNP rs167769: STAT6:c.-22+1137G>A (chr12-57109992-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.-22+1137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,112 control chromosomes in the GnomAD database, including 8,337 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 0.31 ( 8329 hom., cov: 31)

Exomes 𝑓: 0.37 ( 8 hom. )

Consequence

STAT6
NM_003153.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.624

Publications

87 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 = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT6	NM_003153.5 link	c.-22+1137G>A		intron_variant	Intron 1 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.-22+1137G>A		intron_variant	Intron 1 of 21	1	NM_003153.5	ENSP00000300134.3		P42226-1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47175

AN:

151868

Hom.:

8321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.285

GnomAD4 exome

AF:

0.373

AC:

AN:

126

Hom.:

Cov.:

AF XY:

0.344

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.426

AC:

AN:

Other (OTH)

AF:

0.143

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.310

AC:

47185

AN:

151986

Hom.:

8329

Cov.:

AF XY:

0.312

AC XY:

23138

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.146

AC:

6069

AN:

41444

American (AMR)

AF:

0.366

AC:

5584

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1033

AN:

3468

East Asian (EAS)

AF:

0.246

AC:

1275

AN:

5186

South Asian (SAS)

AF:

0.352

AC:

1695

AN:

4812

European-Finnish (FIN)

AF:

0.423

AC:

4464

AN:

10556

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.385

AC:

26178

AN:

67936

Other (OTH)

AF:

0.281

AC:

592

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1572

3145

4717

6290

7862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.350

Hom.:

22586

Bravo

AF:

0.302

Asia WGS

AF:

0.305

AC:

1059

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

(source)

DANN

Benign

0.61

PhyloP100

0.62

PromoterAI

0.0036

Neutral

(source)

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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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