rs3024904

Positions:

• chr2-191030476-T-A

Variant summary

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

The NM_003151.4(STAT4):​c.2220+496A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 152,194 control chromosomes in the GnomAD database, including 828 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 0.10 (828 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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]

STAT4-AS1 (HGNC:55764): (STAT4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.2220+496A>T		intron_variant		ENST00000392320.7
STAT4-AS1	NR_136318.1	n.31-409T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.2220+496A>T		intron_variant		1	NM_003151.4	P1
STAT4	ENST00000358470.8	c.2220+496A>T		intron_variant		1		P1
STAT4-AS1	ENST00000456176.5	n.31-409T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15172 AN: 152076 Hom.: 828 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0997 AC: 15176 AN: 152194 Hom.: 828 Cov.: 32 AF XY: 0.0978 AC XY: 7274 AN XY: 74406

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0803

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.111

Alfa AF: 0.102 Hom.: 123

Bravo AF: 0.0998

Asia WGS AF: 0.125 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.55

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: rs3024904; hg19: chr2-191895202;