2-191068557-T-C

Variant names:

• chr2-191068557-T-C
• rs13389408
• NM_003151.4:c.544+1136A>G

Variant summary

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

The NM_003151.4(STAT4):​c.544+1136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 152,228 control chromosomes in the GnomAD database, including 575 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 0.074 (575 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 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.544+1136A>G		intron	N/A	NP_003142.1
	STAT4	NM_001243835.2		c.544+1136A>G		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.544+1136A>G		intron	N/A	ENSP00000376134.2
	STAT4	ENST00000358470.8	TSL:1	c.544+1136A>G		intron	N/A	ENSP00000351255.4
	STAT4	ENST00000450994.2	TSL:1	c.544+1136A>G		intron	N/A	ENSP00000412397.2

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 11235 AN: 152110 Hom.: 576 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0875

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0738 AC: 11229 AN: 152228 Hom.: 575 Cov.: 32 AF XY: 0.0700 AC XY: 5207 AN XY: 74428

African (AFR) AF: 0.0256 AC: 1064 AN: 41572

American (AMR) AF: 0.0971 AC: 1483 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0842 AC: 292 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0418 AC: 202 AN: 4828

European-Finnish (FIN) AF: 0.0280 AC: 297 AN: 10616

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7596 AN: 67956

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0895 Hom.: 160

Bravo AF: 0.0761

Asia WGS AF: 0.0210 AC: 75 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.64
PhyloP100		0.47
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: rs13389408; hg19: chr2-191933283;