rs12991409

chr2-191144791-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003151.4(STAT4):c.273+1822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 152,202 control chromosomes in the GnomAD database, including 550 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 0.081 (550 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.273+1822A>G		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.273+1822A>G		intron_variant		1	NM_003151.4	P1

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12343 AN: 152082 Hom.: 547 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0812 AC: 12359 AN: 152202 Hom.: 550 Cov.: 32 AF XY: 0.0797 AC XY: 5933 AN XY: 74418

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0569

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0697 Hom.: 370

Bravo AF: 0.0819

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.1
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs12991409; hg19: chr2-192009517;