dbSNP rs55925192: STAT4:c.174-6189C>T (chr2-191154393-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 ENST00000714287.1(STAT4):c.174-6189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,872 control chromosomes in the GnomAD database, including 24,935 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 0.56 ( 24935 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

STAT4
ENST00000714287.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.317

Publications

4 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:

ENSG00000280083 (HGNC:):

ENSG00000280083 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=-0.94).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 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
STAT4	ENST00000714287.1		c.174-6189C>T	intron	N/A	ENSP00000519567.1
ENSG00000280083	ENST00000623836.1	TSL:6	n.1678C>T	non_coding_transcript_exon	Exon 1 of 1
STAT4	ENST00000714288.1		n.1420C>T	non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84392

AN:

151754

Hom.:

24921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.639

Gnomad OTH

AF:

0.553

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.556

AC:

84451

AN:

151872

Hom.:

24935

Cov.:

AF XY:

0.563

AC XY:

41760

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.353

AC:

14618

AN:

41380

American (AMR)

AF:

0.653

AC:

9952

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

2219

AN:

3468

East Asian (EAS)

AF:

0.422

AC:

2182

AN:

5172

South Asian (SAS)

AF:

0.679

AC:

3265

AN:

4812

European-Finnish (FIN)

AF:

0.641

AC:

6750

AN:

10526

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.639

AC:

43435

AN:

67960

Other (OTH)

AF:

0.551

AC:

1159

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1798

3597

5395

7194

8992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.486

Hom.:

1671

Bravo

AF:

0.544

Asia WGS

AF:

0.541

AC:

1877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

6.5

(source)

DANN

Benign

0.66

PhyloP100

0.32

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over