dbSNP rs2278940: STAT4:c.-2+132G>A (chr2-191151202-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 ENST00000358470.8(STAT4):c.-2+132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 985,528 control chromosomes in the GnomAD database, including 3,034 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 0.075 ( 474 hom., cov: 32)

Exomes 𝑓: 0.077 ( 2560 hom. )

Consequence

STAT4
ENST00000358470.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.103

Publications

7 publications found

Variant links:

Genes affected

STAT4 (HGNC:11365): (signal transducer and activator of transcription 4) 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 is essential for mediating responses to IL12 in lymphocytes, and regulating the differentiation of T helper cells. Mutations in this gene may be associated with systemic lupus erythematosus and rheumatoid arthritis. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011]

STAT4 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
disabling pansclerotic morphea of childhood
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

STAT4 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=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4 link	c.-257G>A		upstream_gene_variant		ENST00000392320.7	NP_003142.1	Q14765

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7 link	c.-257G>A		upstream_gene_variant		1	NM_003151.4	ENSP00000376134.2		Q14765

Frequencies

GnomAD3 genomes

AF:

0.0752

AC:

11440

AN:

152112

Hom.:

474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0902

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0486

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.0647

Gnomad FIN

AF:

0.0419

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0723

Gnomad OTH

AF:

0.0742

GnomAD4 exome

AF:

0.0768

AC:

63965

AN:

833298

Hom.:

2560

Cov.:

AF XY:

0.0769

AC XY:

29581

AN XY:

384872

show subpopulations

African (AFR)

AF:

0.0844

AC:

1333

AN:

15792

American (AMR)

AF:

0.0436

AC:

AN:

986

Ashkenazi Jewish (ASJ)

AF:

0.0456

AC:

235

AN:

5152

East Asian (EAS)

AF:

0.181

AC:

657

AN:

3632

South Asian (SAS)

AF:

0.0628

AC:

1034

AN:

16466

European-Finnish (FIN)

AF:

0.0284

AC:

AN:

282

Middle Eastern (MID)

AF:

0.0820

AC:

133

AN:

1622

European-Non Finnish (NFE)

AF:

0.0764

AC:

58252

AN:

762052

Other (OTH)

AF:

0.0831

AC:

2270

AN:

27314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

4166

8332

12497

16663

20829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2972

5944

8916

11888

14860

<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:

0.0752

AC:

11448

AN:

152230

Hom.:

474

Cov.:

AF XY:

0.0732

AC XY:

5451

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0903

AC:

3749

AN:

41528

American (AMR)

AF:

0.0484

AC:

741

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0444

AC:

154

AN:

3472

East Asian (EAS)

AF:

0.177

AC:

915

AN:

5176

South Asian (SAS)

AF:

0.0645

AC:

311

AN:

4820

European-Finnish (FIN)

AF:

0.0419

AC:

445

AN:

10618

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0723

AC:

4918

AN:

68004

Other (OTH)

AF:

0.0749

AC:

158

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

539

1078

1616

2155

2694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0792

Hom.:

152

Bravo

AF:

0.0767

Asia WGS

AF:

0.103

AC:

357

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.1

(source)

DANN

Benign

0.81

PhyloP100

-0.10

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=300/0

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