rs3024935

chr2-191031328-G-T

Variant summary

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

The NM_003151.4(STAT4):c.2111+122C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 1,069,634 control chromosomes in the GnomAD database, including 2,113 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 0.048 (239 hom., cov: 32)
  • Exomes 𝑓: 0.059 (1874 hom.)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.2111+122C>A		intron_variant		ENST00000392320.7
STAT4-AS1	NR_136318.1	n.243+231G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.2111+122C>A		intron_variant		1	NM_003151.4	P1
STAT4-AS1	ENST00000456176.5	n.243+231G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7286 AN: 152108 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.0583

GnomAD4 exome AF: 0.0593 AC: 54359 AN: 917408 Hom.: 1874 Cov.: 12 AF XY: 0.0586 AC XY: 27080 AN XY: 462110

Gnomad4 AFR exome AF: 0.0131

Gnomad4 AMR exome AF: 0.0451

Gnomad4 ASJ exome AF: 0.0919

Gnomad4 EAS exome AF: 0.0000884

Gnomad4 SAS exome AF: 0.0231

Gnomad4 FIN exome AF: 0.0375

Gnomad4 NFE exome AF: 0.0674

Gnomad4 OTH exome AF: 0.0592

GnomAD4 genome AF: 0.0479 AC: 7289 AN: 152226 Hom.: 239 Cov.: 32 AF XY: 0.0464 AC XY: 3454 AN XY: 74418

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0331

Gnomad4 NFE AF: 0.0712

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0696 Hom.: 481

Bravo AF: 0.0497

Asia WGS AF: 0.0120 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.7
Dann	Benign	0.69

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: rs3024935; hg19: chr2-191896054;