Genetic Variant ENSG00000280083:n.179T>G (chr2-191155892-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000623836.1(ENSG00000280083):n.179T>G variant causes a non coding transcript exon 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

ENSG00000280083
ENST00000623836.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.902

Publications

9 publications found

Variant links:

Genes affected

ENSG00000280083 (HGNC:):

ENSG00000280083 links:

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=-0.87).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ENSG00000280083	ENST00000623836.1 link	n.179T>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
STAT4	ENST00000714287.1 link	c.174-7688T>G	intron_variant	Intron 2 of 24		ENSP00000519567.1
STAT4	ENST00000714286.1 link	n.174-7688T>G	intron_variant	Intron 2 of 25		ENSP00000519566.1
STAT4	ENST00000714288.1 link	n.1017-514T>G	intron_variant	Intron 5 of 6

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over