rs16833215

Positions:

• chr2-191049073-A-G
• chr2-191049073-A-T

Variant summary

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

The NM_003151.4(STAT4):​c.1251+5417T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 150,990 control chromosomes in the GnomAD database, including 9,336 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 0.34 (9336 hom., cov: 29)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT4	NM_003151.4	c.1251+5417T>C		intron_variant		ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.1251+5417T>C		intron_variant		1	NM_003151.4	ENSP00000376134	P1
STAT4	ENST00000358470.8	c.1251+5417T>C		intron_variant		1		ENSP00000351255	P1
	ENST00000658263.1	n.1300+2316A>G		intron_variant, non_coding_transcript_variant
STAT4	ENST00000495849.5	n.1319+5417T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 51724 AN: 150880 Hom.: 9324 Cov.: 29

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.343 AC: 51771 AN: 150990 Hom.: 9336 Cov.: 29 AF XY: 0.345 AC XY: 25440 AN XY: 73776

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.355

Alfa AF: 0.319 Hom.: 10922

Bravo AF: 0.364

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
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: rs16833215; hg19: chr2-191913799;