rs3024847

chr2-191065564-T-Achr2-191065564-T-G

Variant summary

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

The NM_003151.4(STAT4):c.631-606A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,048 control chromosomes in the GnomAD database, including 18,731 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 (18731 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.631-606A>T		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.631-606A>T		intron_variant		1	NM_003151.4	P1
STAT4	ENST00000358470.8	c.631-606A>T		intron_variant		1		P1
STAT4	ENST00000495849.5	n.699-606A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68165 AN: 151930 Hom.: 18731 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.448 AC: 68153 AN: 152048 Hom.: 18731 Cov.: 32 AF XY: 0.452 AC XY: 33592 AN XY: 74340

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.461

Alfa AF: 0.520 Hom.: 2894

Bravo AF: 0.416

Asia WGS AF: 0.505 AC: 1747 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.8
Dann	Benign	0.19

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: rs3024847; hg19: chr2-191930290;