12-57096708-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_003153.5(STAT6):c.2408C>A(p.Thr803Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,611,536 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 3 hom. )

Consequence

STAT6
NM_003153.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, STAT6

BP4

Computational evidence support a benign effect (MetaRNN=0.00835827).

BP6

Variant 12-57096708-G-T is Benign according to our data. Variant chr12-57096708-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 733916.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT6	NM_003153.5 linkuse as main transcript	c.2408C>A	p.Thr803Asn	missense_variant	22/22	ENST00000300134.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT6	ENST00000300134.8 linkuse as main transcript	c.2408C>A	p.Thr803Asn	missense_variant	22/22	1	NM_003153.5	P1	P42226-1

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

259

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00608

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000455

AC:

113

AN:

248474

Hom.:

AF XY:

0.000312

AC XY:

AN XY:

134642

show subpopulations

Gnomad AFR exome

AF:

0.00650

Gnomad AMR exome

AF:

0.000239

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000176

AC:

257

AN:

1459260

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

726116

show subpopulations

Gnomad4 AFR exome

AF:

0.00682

Gnomad4 AMR exome

AF:

0.000183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.00170

AC:

259

AN:

152276

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00607

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.00199

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.;T;T;.;T

Eigen

Benign

0.043

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.79

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0084

T;T;T;T;T;T

MetaSVM

Uncertain

0.59

MutationAssessor

Benign

0.97

L;.;L;L;.;L

MutationTaster

Benign

0.94

D;D;D;D;N;N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.69

N;N;N;N;N;N

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.019

D;D;D;D;D;D

Polyphen

0.96

P;.;P;P;.;P

Vest4

0.21

MVP

0.92

MPC

0.52

ClinPred

0.11

GERP RS

4.5

Varity_R

0.73

gMVP

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over