ENST00000714287.1:c.173+1914G>A

Variant names:

• chr2-191165665-C-T
• rs1869624
• ENST00000714287.1:c.173+1914G>A

Variant summary

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

The ENST00000714287.1(STAT4):​c.173+1914G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,100 control chromosomes in the GnomAD database, including 5,214 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 0.25 (5214 hom., cov: 32)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 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.173+1914G>A		intron_variant	Intron 2 of 24			ENSP00000519567.1
STAT4	ENST00000714286.1	n.173+1914G>A		intron_variant	Intron 2 of 25			ENSP00000519566.1
STAT4	ENST00000714288.1	n.1016+1914G>A		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38271 AN: 151982 Hom.: 5216 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.252 AC: 38274 AN: 152100 Hom.: 5214 Cov.: 32 AF XY: 0.244 AC XY: 18147 AN XY: 74346

African (AFR) AF: 0.195 AC: 8082 AN: 41486

American (AMR) AF: 0.227 AC: 3464 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1168 AN: 3472

East Asian (EAS) AF: 0.180 AC: 932 AN: 5172

South Asian (SAS) AF: 0.177 AC: 852 AN: 4820

European-Finnish (FIN) AF: 0.224 AC: 2362 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20602 AN: 67980

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.282 Hom.: 6537

Bravo AF: 0.249

Asia WGS AF: 0.164 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.16
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs1869624; hg19: chr2-192030391;