rs10181656

Variant names:

• chr2-191105153-G-C
• rs10181656
• NM_003151.4:c.274-28828C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-191105153-G-C
• chr2-191105153-G-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.274-28828C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,170 control chromosomes in the GnomAD database, including 46,733 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 0.78 (46733 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 76 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	NM_003151.4	MANE Select	c.274-28828C>G		intron	N/A	NP_003142.1	Q14765
	STAT4	NM_001243835.2		c.274-28828C>G		intron	N/A	NP_001230764.1	Q14765

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	ENST00000392320.7	TSL:1 MANE Select	c.274-28828C>G		intron	N/A	ENSP00000376134.2	Q14765
	STAT4	ENST00000358470.8	TSL:1	c.274-28828C>G		intron	N/A	ENSP00000351255.4	Q14765
	STAT4	ENST00000450994.2	TSL:1	c.274-28828C>G		intron	N/A	ENSP00000412397.2	Q14765

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118793 AN: 152052 Hom.: 46696 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.781 AC: 118878 AN: 152170 Hom.: 46733 Cov.: 32 AF XY: 0.778 AC XY: 57868 AN XY: 74396

African (AFR) AF: 0.853 AC: 35450 AN: 41544

American (AMR) AF: 0.691 AC: 10551 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2613 AN: 3468

East Asian (EAS) AF: 0.645 AC: 3335 AN: 5172

South Asian (SAS) AF: 0.713 AC: 3440 AN: 4826

European-Finnish (FIN) AF: 0.769 AC: 8133 AN: 10574

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52785 AN: 67994

Other (OTH) AF: 0.767 AC: 1619 AN: 2112

Alfa AF: 0.787 Hom.: 5886

Bravo AF: 0.778

Asia WGS AF: 0.666 AC: 2314 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	3.2
DANN	Benign	0.60
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10181656; hg19: chr2-191969879;