rs4853550

Variant names:

• chr2-191166501-G-T
• rs4853550
• ENST00000714287.1:c.173+1078C>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+1078C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,128 control chromosomes in the GnomAD database, including 37,431 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 0.68 (37431 hom., cov: 33)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 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+1078C>A		intron	N/A	ENSP00000519567.1	A0AAQ5BHW3
	STAT4	ENST00000714286.1		n.173+1078C>A		intron	N/A	ENSP00000519566.1	A0AAQ5BHR1
	STAT4	ENST00000714288.1		n.1016+1078C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103552 AN: 152010 Hom.: 37419 Cov.: 33

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.681 AC: 103610 AN: 152128 Hom.: 37431 Cov.: 33 AF XY: 0.682 AC XY: 50714 AN XY: 74364

African (AFR) AF: 0.440 AC: 18236 AN: 41472

American (AMR) AF: 0.775 AC: 11847 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2979 AN: 3472

East Asian (EAS) AF: 0.444 AC: 2300 AN: 5184

South Asian (SAS) AF: 0.774 AC: 3737 AN: 4826

European-Finnish (FIN) AF: 0.743 AC: 7845 AN: 10554

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54145 AN: 68018

Other (OTH) AF: 0.720 AC: 1519 AN: 2110

Alfa AF: 0.756 Hom.: 64190

Bravo AF: 0.672

Asia WGS AF: 0.609 AC: 2120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.33
PhyloP100		0.034

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4853550;

hg19: chr2-192031227;