Genetic Variant STAT4:c.2111+122C>A (chr2-191031328-G-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_003151.4(STAT4):c.2111+122C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 1,069,634 control chromosomes in the GnomAD database, including 2,113 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 0.048 ( 239 hom., cov: 32)

Exomes 𝑓: 0.059 ( 1874 hom. )

Consequence

STAT4
NM_003151.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.457

Publications

11 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 links:

STAT4-AS1 (HGNC:55764): (STAT4 antisense RNA 1)

STAT4-AS1 links:

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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 = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4 link	c.2111+122C>A		intron_variant	Intron 22 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7 link	c.2111+122C>A		intron_variant	Intron 22 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes

AF:

0.0479

AC:

7286

AN:

152108

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0524

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0331

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0712

Gnomad OTH

AF:

0.0583

GnomAD4 exome

AF:

0.0593

AC:

54359

AN:

917408

Hom.:

1874

Cov.:

AF XY:

0.0586

AC XY:

27080

AN XY:

462110

show subpopulations

African (AFR)

AF:

0.0131

AC:

278

AN:

21144

American (AMR)

AF:

0.0451

AC:

974

AN:

21584

Ashkenazi Jewish (ASJ)

AF:

0.0919

AC:

1609

AN:

17506

East Asian (EAS)

AF:

0.0000884

AC:

AN:

33946

South Asian (SAS)

AF:

0.0231

AC:

1315

AN:

56870

European-Finnish (FIN)

AF:

0.0375

AC:

1657

AN:

44170

Middle Eastern (MID)

AF:

0.119

AC:

482

AN:

4050

European-Non Finnish (NFE)

AF:

0.0674

AC:

45590

AN:

676730

Other (OTH)

AF:

0.0592

AC:

2451

AN:

41408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2499

4999

7498

9998

12497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1382

2764

4146

5528

6910

<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:

0.0479

AC:

7289

AN:

152226

Hom.:

239

Cov.:

AF XY:

0.0464

AC XY:

3454

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0150

AC:

624

AN:

41554

American (AMR)

AF:

0.0524

AC:

801

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

348

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0228

AC:

110

AN:

4824

European-Finnish (FIN)

AF:

0.0331

AC:

350

AN:

10588

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0712

AC:

4844

AN:

67990

Other (OTH)

AF:

0.0572

AC:

121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

356

712

1068

1424

1780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0686

Hom.:

542

Bravo

AF:

0.0497

Asia WGS

AF:

0.0120

AC:

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

4.7

(source)

DANN

Benign

0.69

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism

(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