2-191168974-A-T

Variant names:

• chr2-191168974-A-T
• rs2054090
• ENST00000714287.1:c.27-1249T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000714287.1(STAT4):​c.27-1249T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,072 control chromosomes in the GnomAD database, including 13,323 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 0.37 (13323 hom., cov: 32)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000714287.1	c.27-1249T>A		intron_variant	Intron 1 of 24			ENSP00000519567.1
STAT4	ENST00000714286.1	n.27-1249T>A		intron_variant	Intron 1 of 25			ENSP00000519566.1
STAT4	ENST00000714288.1	n.748-338T>A		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56163 AN: 151954 Hom.: 13280 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56264 AN: 152072 Hom.: 13323 Cov.: 32 AF XY: 0.363 AC XY: 26978 AN XY: 74332

African (AFR) AF: 0.682 AC: 28313 AN: 41486

American (AMR) AF: 0.260 AC: 3979 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2081 AN: 5172

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2442 AN: 10564

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16391 AN: 67970

Other (OTH) AF: 0.358 AC: 755 AN: 2108

Alfa AF: 0.308 Hom.: 1171

Bravo AF: 0.389

Asia WGS AF: 0.388 AC: 1344 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.73
PhyloP100		-0.38

Splicing

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

Other links and lift over

dbSNP: rs2054090; hg19: chr2-192033700;