chr2-191159824-T-C

Variant names:

• chr2-191159824-T-C
• rs16833453
• ENST00000714287.1:c.173+7755A>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+7755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,802 control chromosomes in the GnomAD database, including 24,901 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 0.56 (24901 hom., cov: 30)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 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+7755A>G		intron	N/A	ENSP00000519567.1	A0AAQ5BHW3
	STAT4	ENST00000714286.1		n.173+7755A>G		intron	N/A	ENSP00000519566.1	A0AAQ5BHR1
	STAT4	ENST00000714288.1		n.1017-4446A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84336 AN: 151684 Hom.: 24886 Cov.: 30

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.556 AC: 84397 AN: 151802 Hom.: 24901 Cov.: 30 AF XY: 0.563 AC XY: 41744 AN XY: 74178

African (AFR) AF: 0.355 AC: 14688 AN: 41336

American (AMR) AF: 0.651 AC: 9942 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2198 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2173 AN: 5136

South Asian (SAS) AF: 0.680 AC: 3265 AN: 4804

European-Finnish (FIN) AF: 0.641 AC: 6751 AN: 10540

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.638 AC: 43356 AN: 67926

Other (OTH) AF: 0.548 AC: 1155 AN: 2108

Alfa AF: 0.593 Hom.: 3559

Bravo AF: 0.544

Asia WGS AF: 0.542 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.65

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: rs16833453;

hg19: chr2-192024550;