2-191108837-A-G

Variant names:

• chr2-191108837-A-G
• rs6752770
• NM_003151.4:c.274-32512T>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.274-32512T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,096 control chromosomes in the GnomAD database, including 7,289 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 0.30 (7289 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 51 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 (AFR) allele frequency at 95% confidence interval = 0.362 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.274-32512T>C		intron	N/A	NP_003142.1
	STAT4	NM_001243835.2		c.274-32512T>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.274-32512T>C		intron	N/A	ENSP00000376134.2
	STAT4	ENST00000358470.8	TSL:1	c.274-32512T>C		intron	N/A	ENSP00000351255.4
	STAT4	ENST00000450994.2	TSL:1	c.274-32512T>C		intron	N/A	ENSP00000412397.2

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46107 AN: 151978 Hom.: 7279 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.303 AC: 46138 AN: 152096 Hom.: 7289 Cov.: 32 AF XY: 0.299 AC XY: 22264 AN XY: 74372

African (AFR) AF: 0.367 AC: 15197 AN: 41452

American (AMR) AF: 0.310 AC: 4746 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1213 AN: 5186

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4826

European-Finnish (FIN) AF: 0.204 AC: 2164 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19918 AN: 67966

Other (OTH) AF: 0.303 AC: 639 AN: 2112

Alfa AF: 0.297 Hom.: 11555

Bravo AF: 0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.46
DANN	Benign	0.56
PhyloP100		-0.69
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: rs6752770; hg19: chr2-191973563;