chr2-191034223-C-T

Variant names:

• chr2-191034223-C-T
• rs3024891
• NM_003151.4:c.1621-218G>A

Variant summary

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

The NM_003151.4(STAT4):​c.1621-218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,856 control chromosomes in the GnomAD database, including 11,634 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 0.36 (11634 hom., cov: 30)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.1621-218G>A		intron_variant	Intron 18 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.1621-218G>A		intron_variant	Intron 18 of 23	1	NM_003151.4	ENSP00000376134.2
STAT4	ENST00000358470.8	c.1621-218G>A		intron_variant	Intron 18 of 23	1		ENSP00000351255.4
STAT4	ENST00000495849.5	n.1689-218G>A		intron_variant	Intron 18 of 20	2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53995 AN: 151738 Hom.: 11638 Cov.: 30

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.356 AC: 53990 AN: 151856 Hom.: 11634 Cov.: 30 AF XY: 0.354 AC XY: 26311 AN XY: 74250

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.346

Alfa AF: 0.302 Hom.: 905

Bravo AF: 0.336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.77
DANN	Benign	0.41

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: rs3024891; hg19: chr2-191898949;