rs7574070

Variant names:

• chr2-191145762-A-C
• rs7574070
• NM_003151.4:c.273+851T>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.273+851T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,112 control chromosomes in the GnomAD database, including 25,171 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 0.55 (25171 hom., cov: 33)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 45 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.273+851T>G		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+851T>G		intron_variant	Intron 3 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83775 AN: 151994 Hom.: 25163 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.551 AC: 83810 AN: 152112 Hom.: 25171 Cov.: 33 AF XY: 0.556 AC XY: 41360 AN XY: 74350

African (AFR) AF: 0.302 AC: 12519 AN: 41508

American (AMR) AF: 0.654 AC: 9999 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2221 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2193 AN: 5174

South Asian (SAS) AF: 0.684 AC: 3303 AN: 4828

European-Finnish (FIN) AF: 0.643 AC: 6786 AN: 10552

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44713 AN: 67976

Other (OTH) AF: 0.554 AC: 1168 AN: 2110

Alfa AF: 0.606 Hom.: 43852

Bravo AF: 0.538

Asia WGS AF: 0.540 AC: 1874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		0.052
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: rs7574070; hg19: chr2-192010488;