Genetic Variant ENSG00000280083:n.1678C>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 ENST00000623836.1(ENSG00000280083):n.1678C>T 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 0.556 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

ENSG00000280083
ENST00000623836.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.317

Publications

4 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=-0.94).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 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.1678C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
STAT4	ENST00000714288.1 link	n.1420C>T	non_coding_transcript_exon_variant	Exon 7 of 7
STAT4	ENST00000714287.1 link	c.174-6189C>T	intron_variant	Intron 2 of 24		ENSP00000519567.1
STAT4	ENST00000714286.1 link	n.174-6189C>T	intron_variant	Intron 2 of 25		ENSP00000519566.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over