chr2-191039830-A-G

Variant names:

• chr2-191039830-A-G
• rs3024879
• NM_003151.4:c.1336-533T>C

Variant summary

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

The NM_003151.4(STAT4):​c.1336-533T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,182 control chromosomes in the GnomAD database, including 58,313 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 0.86 (58313 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003151.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	NM_003151.4	MANE Select	c.1336-533T>C		intron	N/A	NP_003142.1
	STAT4	NM_001243835.2		c.1336-533T>C		intron	N/A	NP_001230764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	ENST00000392320.7	TSL:1 MANE Select	c.1336-533T>C		intron	N/A	ENSP00000376134.2
	STAT4	ENST00000358470.8	TSL:1	c.1336-533T>C		intron	N/A	ENSP00000351255.4
	STAT4	ENST00000450994.2	TSL:1	c.1336-533T>C		intron	N/A	ENSP00000412397.2

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131471 AN: 152064 Hom.: 58302 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.864 AC: 131530 AN: 152182 Hom.: 58313 Cov.: 32 AF XY: 0.869 AC XY: 64637 AN XY: 74404

African (AFR) AF: 0.638 AC: 26442 AN: 41448

American (AMR) AF: 0.919 AC: 14066 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3246 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5172 AN: 5184

South Asian (SAS) AF: 0.950 AC: 4589 AN: 4828

European-Finnish (FIN) AF: 0.967 AC: 10254 AN: 10606

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.952 AC: 64736 AN: 68028

Other (OTH) AF: 0.883 AC: 1865 AN: 2112

Alfa AF: 0.812 Hom.: 18740

Bravo AF: 0.850

Asia WGS AF: 0.952 AC: 3309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.60
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3024879; hg19: chr2-191904556;