dbSNP rs1031507: STAT4:c.174-7688T>G (chr2-191155892-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000714287.1(STAT4):c.174-7688T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,100 control chromosomes in the GnomAD database, including 25,972 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 0.57 ( 25970 hom., cov: 32)

Exomes 𝑓: 0.44 ( 2 hom. )

Consequence

STAT4
ENST00000714287.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.902

Publications

9 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):

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

STAT4 links:

ENSG00000280083 (HGNC:):

ENSG00000280083 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000714287.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714287.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STAT4	ENST00000714287.1		c.174-7688T>G	intron	N/A	ENSP00000519567.1	A0AAQ5BHW3
ENSG00000280083	ENST00000623836.1	TSL:6	n.179T>G	non_coding_transcript_exon	Exon 1 of 1
STAT4	ENST00000714286.1		n.174-7688T>G	intron	N/A	ENSP00000519566.1	A0AAQ5BHR1

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

86086

AN:

151964

Hom.:

25953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.832

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.643

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.564

GnomAD4 exome

AF:

0.444

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.566

AC:

86148

AN:

152082

Hom.:

25970

Cov.:

AF XY:

0.572

AC XY:

42524

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.356

AC:

14777

AN:

41458

American (AMR)

AF:

0.660

AC:

10092

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

2219

AN:

3464

East Asian (EAS)

AF:

0.422

AC:

2179

AN:

5166

South Asian (SAS)

AF:

0.682

AC:

3292

AN:

4826

European-Finnish (FIN)

AF:

0.643

AC:

6784

AN:

10554

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.658

AC:

44713

AN:

67996

Other (OTH)

AF:

0.561

AC:

1185

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1792

3585

5377

7170

8962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.609

Hom.:

3884

Bravo

AF:

0.556

Asia WGS

AF:

0.543

AC:

1885

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.72

PhyloP100

-0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over