2-191131792-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+14821A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,340,730 control chromosomes in the GnomAD database, including 274,272 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 0.63 (31240 hom., cov: 32)
  • Exomes 𝑓: 0.64 (243032 hom.)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.273+14821A>G		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.273+14821A>G		intron_variant		1	NM_003151.4	P1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96014 AN: 151296 Hom.: 31203 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.626

GnomAD3 exomes AF: 0.677 AC: 23378 AN: 34520 Hom.: 8102 AF XY: 0.677 AC XY: 12160 AN XY: 17972

Gnomad AFR exome AF: 0.549

Gnomad AMR exome AF: 0.781

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.681

Gnomad SAS exome AF: 0.739

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.645

GnomAD4 exome AF: 0.637 AC: 757042 AN: 1189316 Hom.: 243032 Cov.: 35 AF XY: 0.638 AC XY: 366709 AN XY: 574648

Gnomad4 AFR exome AF: 0.576

Gnomad4 AMR exome AF: 0.738

Gnomad4 ASJ exome AF: 0.589

Gnomad4 EAS exome AF: 0.763

Gnomad4 SAS exome AF: 0.740

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.635 AC: 96097 AN: 151414 Hom.: 31240 Cov.: 32 AF XY: 0.642 AC XY: 47528 AN XY: 73982

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.628

Alfa AF: 0.622 Hom.: 60882

Bravo AF: 0.628

Asia WGS AF: 0.749 AC: 2602 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	15
Dann	Benign	0.80

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: rs1551443; hg19: chr2-191996518;