rs1400654

Variant names:

• chr2-191050947-T-A
• rs1400654
• NM_003151.4:c.1251+3543A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-191050947-T-A
• chr2-191050947-T-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.1251+3543A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,186 control chromosomes in the GnomAD database, including 51,008 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 (51008 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 5 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

ENSG00000288064 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.1251+3543A>T		intron_variant	Intron 14 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.1251+3543A>T		intron_variant	Intron 14 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118628 AN: 152068 Hom.: 50994 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.780 AC: 118660 AN: 152186 Hom.: 51008 Cov.: 32 AF XY: 0.786 AC XY: 58463 AN XY: 74426

African (AFR) AF: 0.377 AC: 15641 AN: 41458

American (AMR) AF: 0.882 AC: 13491 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3146 AN: 3470

East Asian (EAS) AF: 0.915 AC: 4740 AN: 5180

South Asian (SAS) AF: 0.896 AC: 4327 AN: 4828

European-Finnish (FIN) AF: 0.959 AC: 10180 AN: 10614

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64291 AN: 68024

Other (OTH) AF: 0.825 AC: 1744 AN: 2114

Alfa AF: 0.851 Hom.: 7247

Bravo AF: 0.756

Asia WGS AF: 0.883 AC: 3073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.46
PhyloP100		0.076
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: rs1400654; hg19: chr2-191915673;