Genetic Variant STAT4:c.174-6442A>C (chr2-191154646-T-G) – 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.174-6442A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 150,350 control chromosomes in the GnomAD database, including 23,114 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 0.52 ( 23113 hom., cov: 32)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

STAT4
ENST00000714287.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.282

Publications

8 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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.671 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.174-6442A>C	intron	N/A	ENSP00000519567.1	A0AAQ5BHW3
ENSG00000280083	ENST00000623836.1	TSL:6	n.1425A>C	non_coding_transcript_exon	Exon 1 of 1
STAT4	ENST00000714286.1		n.174-6442A>C	intron	N/A	ENSP00000519566.1	A0AAQ5BHR1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

77763

AN:

150234

Hom.:

23113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.792

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.691

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.525

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

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)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.517

AC:

77775

AN:

150346

Hom.:

23113

Cov.:

AF XY:

0.525

AC XY:

38547

AN XY:

73470

show subpopulations

African (AFR)

AF:

0.210

AC:

8688

AN:

41402

American (AMR)

AF:

0.641

AC:

9717

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

2213

AN:

3452

East Asian (EAS)

AF:

0.422

AC:

2180

AN:

5164

South Asian (SAS)

AF:

0.690

AC:

3220

AN:

4664

European-Finnish (FIN)

AF:

0.652

AC:

6695

AN:

10272

Middle Eastern (MID)

AF:

0.503

AC:

147

AN:

292

European-Non Finnish (NFE)

AF:

0.644

AC:

43098

AN:

66944

Other (OTH)

AF:

0.523

AC:

1095

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1660

3319

4979

6638

8298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.574

Hom.:

9125

Bravo

AF:

0.499

Asia WGS

AF:

0.528

AC:

1832

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.9

(source)

DANN

Benign

0.51

PhyloP100

-0.28

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over