rs7596818

Positions:

• chr2-191144584-G-A

Variant summary

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

The NM_003151.4(STAT4):​c.273+2029C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 149,554 control chromosomes in the GnomAD database, including 1,632 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 0.13 (1632 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927

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 (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.273+2029C>T		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.273+2029C>T		intron_variant		1	NM_003151.4	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 19829 AN: 149438 Hom.: 1624 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.133 AC: 19850 AN: 149554 Hom.: 1632 Cov.: 31 AF XY: 0.131 AC XY: 9573 AN XY: 72834

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.143

Alfa AF: 0.110 Hom.: 1472

Bravo AF: 0.142

Asia WGS AF: 0.185 AC: 628 AN: 3390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.70

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: rs7596818; hg19: chr2-192009310;