rs10804037

Variant names:

• chr2-191127165-C-A
• rs10804037
• NM_003151.4:c.273+19448G>T

Variant summary

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

The NM_003151.4(STAT4):​c.273+19448G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,868 control chromosomes in the GnomAD database, including 28,969 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 0.61 (28969 hom., cov: 30)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 4 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

ENSG00000300654 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.76 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.273+19448G>T		intron	N/A	NP_003142.1
	STAT4	NM_001243835.2		c.273+19448G>T		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.273+19448G>T		intron	N/A	ENSP00000376134.2
	STAT4	ENST00000358470.8	TSL:1	c.273+19448G>T		intron	N/A	ENSP00000351255.4
	STAT4	ENST00000450994.2	TSL:1	c.273+19448G>T		intron	N/A	ENSP00000412397.2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92473 AN: 151750 Hom.: 28934 Cov.: 30

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.609 AC: 92551 AN: 151868 Hom.: 28969 Cov.: 30 AF XY: 0.619 AC XY: 45919 AN XY: 74226

African (AFR) AF: 0.477 AC: 19727 AN: 41366

American (AMR) AF: 0.696 AC: 10648 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2058 AN: 3468

East Asian (EAS) AF: 0.742 AC: 3822 AN: 5154

South Asian (SAS) AF: 0.780 AC: 3763 AN: 4822

European-Finnish (FIN) AF: 0.721 AC: 7594 AN: 10538

Middle Eastern (MID) AF: 0.555 AC: 161 AN: 290

European-Non Finnish (NFE) AF: 0.630 AC: 42775 AN: 67922

Other (OTH) AF: 0.608 AC: 1281 AN: 2108

Alfa AF: 0.626 Hom.: 3778

Bravo AF: 0.600

Asia WGS AF: 0.778 AC: 2705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.98
DANN	Benign	0.78
PhyloP100		-1.1
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: rs10804037; hg19: chr2-191991891;