dbSNP rs3024974: STAT6:c.1955+53C>T (chr12-57098962-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.1955+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,612,824 control chromosomes in the GnomAD database, including 7,910 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 0.10 ( 845 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7065 hom. )

Consequence

STAT6
NM_003153.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.560

Publications

38 publications found

Variant links:

COSMIC-nc: COSV55665564

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 (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT6	NM_003153.5 link	c.1955+53C>T		intron_variant	Intron 17 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.1955+53C>T		intron_variant	Intron 17 of 21	1	NM_003153.5	ENSP00000300134.3		P42226-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15608

AN:

151960

Hom.:

840

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0965

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0926

Gnomad OTH

AF:

0.0995

GnomAD4 exome

AF:

0.0961

AC:

140444

AN:

1460746

Hom.:

7065

Cov.:

AF XY:

0.0963

AC XY:

69972

AN XY:

726780

show subpopulations

African (AFR)

AF:

0.0967

AC:

3235

AN:

33464

American (AMR)

AF:

0.0960

AC:

4294

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0893

AC:

2333

AN:

26124

East Asian (EAS)

AF:

0.160

AC:

6339

AN:

39688

South Asian (SAS)

AF:

0.107

AC:

9224

AN:

86232

European-Finnish (FIN)

AF:

0.112

AC:

5966

AN:

53420

Middle Eastern (MID)

AF:

0.106

AC:

610

AN:

5766

European-Non Finnish (NFE)

AF:

0.0923

AC:

102576

AN:

1110972

Other (OTH)

AF:

0.0972

AC:

5867

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7539

15079

22618

30158

37697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3814

7628

11442

15256

19070

<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:

0.103

AC:

15651

AN:

152078

Hom.:

845

Cov.:

AF XY:

0.105

AC XY:

7821

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0972

AC:

4026

AN:

41438

American (AMR)

AF:

0.128

AC:

1947

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0878

AC:

305

AN:

3472

East Asian (EAS)

AF:

0.198

AC:

1023

AN:

5174

South Asian (SAS)

AF:

0.110

AC:

532

AN:

4824

European-Finnish (FIN)

AF:

0.113

AC:

1196

AN:

10598

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0926

AC:

6298

AN:

67986

Other (OTH)

AF:

0.102

AC:

216

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

723

1446

2168

2891

3614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0945

Hom.:

960

Bravo

AF:

0.102

Asia WGS

AF:

0.171

AC:

594

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

0.80

(source)

DANN

Benign

0.65

PhyloP100

-0.56

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)

0.020

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