2-191029415-T-C

Variant names:

• chr2-191029415-T-C
• rs3024908
• ENST00000456176.5:n.31-1470T>C

Variant summary

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

The NR_136318.1(STAT4-AS1):​n.31-1470T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 152,210 control chromosomes in the GnomAD database, including 826 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 0.10 (826 hom., cov: 32)
• Consequence: STAT4-AS1 NR_136318.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 17 publications found

Genes affected

STAT4-AS1 (HGNC:55764): (STAT4 antisense RNA 1)

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):

• disabling pansclerotic morphea of childhood

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_136318.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4-AS1	NR_136318.1		n.31-1470T>C		intron	N/A
	STAT4	NM_003151.4	MANE Select	c.*425A>G		downstream_gene	N/A	NP_003142.1	Q14765
	STAT4	NM_001243835.2		c.*425A>G		downstream_gene	N/A	NP_001230764.1	Q14765

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4-AS1	ENST00000456176.5	TSL:5	n.31-1470T>C		intron	N/A
	STAT4	ENST00000392320.7	TSL:1 MANE Select	c.*425A>G		downstream_gene	N/A	ENSP00000376134.2	Q14765
	STAT4	ENST00000358470.8	TSL:1	c.*425A>G		downstream_gene	N/A	ENSP00000351255.4	Q14765

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15173 AN: 152092 Hom.: 826 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0997 AC: 15177 AN: 152210 Hom.: 826 Cov.: 32 AF XY: 0.0977 AC XY: 7275 AN XY: 74428

African (AFR) AF: 0.0723 AC: 3002 AN: 41526

American (AMR) AF: 0.104 AC: 1597 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3468

East Asian (EAS) AF: 0.156 AC: 807 AN: 5184

South Asian (SAS) AF: 0.149 AC: 717 AN: 4822

European-Finnish (FIN) AF: 0.0802 AC: 851 AN: 10606

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7347 AN: 67992

Other (OTH) AF: 0.111 AC: 235 AN: 2114

Alfa AF: 0.108 Hom.: 3011

Bravo AF: 0.100

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
DANN	Benign	0.56
PhyloP100		-0.91

Splicing

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

Other links and lift over

dbSNP: rs3024908; hg19: chr2-191894141;