chr2-191034223-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003151.4(STAT4):​c.1621-218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,856 control chromosomes in the GnomAD database, including 11,634 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 0.36 ( 11634 hom., cov: 30)

Consequence

STAT4
NM_003151.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.589
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STAT4NM_003151.4 linkc.1621-218G>A intron_variant Intron 18 of 23 ENST00000392320.7 NP_003142.1 Q14765

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STAT4ENST00000392320.7 linkc.1621-218G>A intron_variant Intron 18 of 23 1 NM_003151.4 ENSP00000376134.2 Q14765
STAT4ENST00000358470.8 linkc.1621-218G>A intron_variant Intron 18 of 23 1 ENSP00000351255.4 Q14765
STAT4ENST00000495849.5 linkn.1689-218G>A intron_variant Intron 18 of 20 2

Frequencies

GnomAD3 genomes
AF:
0.356
AC:
53995
AN:
151738
Hom.:
11638
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.131
Gnomad AMI
AF:
0.535
Gnomad AMR
AF:
0.336
Gnomad ASJ
AF:
0.359
Gnomad EAS
AF:
0.160
Gnomad SAS
AF:
0.396
Gnomad FIN
AF:
0.482
Gnomad MID
AF:
0.245
Gnomad NFE
AF:
0.488
Gnomad OTH
AF:
0.348
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.356
AC:
53990
AN:
151856
Hom.:
11634
Cov.:
30
AF XY:
0.354
AC XY:
26311
AN XY:
74250
show subpopulations
Gnomad4 AFR
AF:
0.131
Gnomad4 AMR
AF:
0.336
Gnomad4 ASJ
AF:
0.359
Gnomad4 EAS
AF:
0.159
Gnomad4 SAS
AF:
0.396
Gnomad4 FIN
AF:
0.482
Gnomad4 NFE
AF:
0.488
Gnomad4 OTH
AF:
0.346
Alfa
AF:
0.302
Hom.:
905
Bravo
AF:
0.336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.77
DANN
Benign
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3024891; hg19: chr2-191898949; API