2-191083546-C-T

Position:

• chr2-191083546-C-T

Variant summary

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

The ENST00000392320.7(STAT4):​c.274-7221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,080 control chromosomes in the GnomAD database, including 19,174 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 0.45 (19174 hom., cov: 32)
• Consequence: STAT4 ENST00000392320.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT4	NM_003151.4	c.274-7221G>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.274-7221G>A		intron_variant		1	NM_003151.4	ENSP00000376134	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69075 AN: 151962 Hom.: 19175 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.454 AC: 69064 AN: 152080 Hom.: 19174 Cov.: 32 AF XY: 0.461 AC XY: 34246 AN XY: 74346

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.468

Alfa AF: 0.488 Hom.: 4288

Bravo AF: 0.419

Asia WGS AF: 0.516 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.45

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: rs16833249; hg19: chr2-191948272;