rs4583497

Positions:

• chr2-191125380-C-G

Variant summary

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

The NM_003151.4(STAT4):​c.273+21233G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,540 control chromosomes in the GnomAD database, including 26,419 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 0.57 (26419 hom., cov: 30)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.273+21233G>C		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.273+21233G>C		intron_variant		1	NM_003151.4	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87066 AN: 151424 Hom.: 26396 Cov.: 30

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.575 AC: 87107 AN: 151540 Hom.: 26419 Cov.: 30 AF XY: 0.584 AC XY: 43218 AN XY: 74058

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.576

Alfa AF: 0.607 Hom.: 3614

Bravo AF: 0.560

Asia WGS AF: 0.734 AC: 2550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.68

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: rs4583497; hg19: chr2-191990106;