2-191166537-T-C

Variant names:

• chr2-191166537-T-C
• rs4853551
• ENST00000714287.1:c.173+1042A>G

Variant summary

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

The ENST00000714287.1(STAT4):​c.173+1042A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,216 control chromosomes in the GnomAD database, including 55,363 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 0.84 (55363 hom., cov: 32)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 3 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):

• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714287.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	ENST00000714287.1		c.173+1042A>G		intron	N/A	ENSP00000519567.1	A0AAQ5BHW3
	STAT4	ENST00000714286.1		n.173+1042A>G		intron	N/A	ENSP00000519566.1	A0AAQ5BHR1
	STAT4	ENST00000714288.1		n.1016+1042A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128477 AN: 152098 Hom.: 55342 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.844 AC: 128539 AN: 152216 Hom.: 55363 Cov.: 32 AF XY: 0.848 AC XY: 63114 AN XY: 74412

African (AFR) AF: 0.656 AC: 27194 AN: 41482

American (AMR) AF: 0.900 AC: 13771 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3270 AN: 3470

East Asian (EAS) AF: 0.894 AC: 4639 AN: 5188

South Asian (SAS) AF: 0.923 AC: 4456 AN: 4826

European-Finnish (FIN) AF: 0.941 AC: 9984 AN: 10610

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62269 AN: 68024

Other (OTH) AF: 0.863 AC: 1825 AN: 2114

Alfa AF: 0.889 Hom.: 90042

Bravo AF: 0.833

Asia WGS AF: 0.888 AC: 3090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.50
PhyloP100		0.077

Splicing

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

Other links and lift over

dbSNP: rs4853551; hg19: chr2-192031263;