rs2278940

Positions:

• chr2-191151202-C-T

Variant summary

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

The NM_001243835.2(STAT4):​c.-2+132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 985,528 control chromosomes in the GnomAD database, including 3,034 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 0.075 (474 hom., cov: 32)
  • Exomes 𝑓: 0.077 (2560 hom.)
• Consequence: STAT4 NM_001243835.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT4	NM_001243835.2	c.-2+132G>A		intron_variant			NP_001230764.1
STAT4	XM_047445603.1	c.-84+132G>A		intron_variant			XP_047301559.1
STAT4	XM_047445604.1	c.-70+132G>A		intron_variant			XP_047301560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000358470.8	c.-2+132G>A		intron_variant		1		ENSP00000351255.4
STAT4	ENST00000450994.1	c.-70+132G>A		intron_variant		1		ENSP00000412397.2
STAT4	ENST00000413064.5	c.-31+132G>A		intron_variant		5		ENSP00000403238.2

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11440 AN: 152112 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0647

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.0768 AC: 63965 AN: 833298 Hom.: 2560 Cov.: 30 AF XY: 0.0769 AC XY: 29581 AN XY: 384872

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.0436

Gnomad4 ASJ exome AF: 0.0456

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.0628

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0764

Gnomad4 OTH exome AF: 0.0831

GnomAD4 genome AF: 0.0752 AC: 11448 AN: 152230 Hom.: 474 Cov.: 32 AF XY: 0.0732 AC XY: 5451 AN XY: 74438

Gnomad4 AFR AF: 0.0903

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.0645

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0723

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0700 Hom.: 59

Bravo AF: 0.0767

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.81

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: rs2278940; hg19: chr2-192015928;