2-191032814-C-T

Position:

• chr2-191032814-C-T

Variant summary

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

The NM_003151.4(STAT4):​c.2044+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 824,180 control chromosomes in the GnomAD database, including 37,585 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 0.32 (7967 hom., cov: 32)
  • Exomes 𝑓: 0.29 (29618 hom.)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT4	NM_003151.4	c.2044+144G>A		intron_variant		ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.2044+144G>A		intron_variant		1	NM_003151.4	ENSP00000376134.2
STAT4	ENST00000358470.8	c.2044+144G>A		intron_variant		1		ENSP00000351255.4
STAT4	ENST00000463951.1	n.310+144G>A		intron_variant		4
STAT4	ENST00000495849.5	n.*48G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48117 AN: 151882 Hom.: 7965 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.289 AC: 194347 AN: 672180 Hom.: 29618 Cov.: 9 AF XY: 0.289 AC XY: 99194 AN XY: 343054

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.317 AC: 48137 AN: 152000 Hom.: 7967 Cov.: 32 AF XY: 0.317 AC XY: 23551 AN XY: 74312

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.341

Alfa AF: 0.285 Hom.: 8629

Bravo AF: 0.324

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.79

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: rs925847; hg19: chr2-191897540;