rs4853546

Variant names:

• chr2-191144926-A-G
• rs4853546
• NM_003151.4:c.273+1687T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-191144926-A-G
• chr2-191144926-A-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+1687T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,926 control chromosomes in the GnomAD database, including 28,692 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 0.60 (28692 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.273+1687T>C		intron_variant	Intron 3 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.273+1687T>C		intron_variant	Intron 3 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91159 AN: 151808 Hom.: 28678 Cov.: 31

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.600 AC: 91212 AN: 151926 Hom.: 28692 Cov.: 31 AF XY: 0.610 AC XY: 45328 AN XY: 74266

African (AFR) AF: 0.406 AC: 16808 AN: 41398

American (AMR) AF: 0.652 AC: 9951 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2135 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3321 AN: 5172

South Asian (SAS) AF: 0.755 AC: 3632 AN: 4812

European-Finnish (FIN) AF: 0.773 AC: 8152 AN: 10542

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45140 AN: 67948

Other (OTH) AF: 0.581 AC: 1224 AN: 2108

Alfa AF: 0.636 Hom.: 36537

Bravo AF: 0.580

Asia WGS AF: 0.670 AC: 2328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.041
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: rs4853546; hg19: chr2-192009652;