rs10497711

chr2-191149195-A-G

Variant summary

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

The NM_003151.4(STAT4):c.-1-991T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,214 control chromosomes in the GnomAD database, including 442 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 0.072 (442 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.-1-991T>C		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.-1-991T>C		intron_variant		1	NM_003151.4	P1

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10984 AN: 152096 Hom.: 442 Cov.: 32

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0722 AC: 10985 AN: 152214 Hom.: 442 Cov.: 32 AF XY: 0.0700 AC XY: 5209 AN XY: 74398

Gnomad4 AFR AF: 0.0797

Gnomad4 AMR AF: 0.0475

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.0416

Gnomad4 NFE AF: 0.0723

Gnomad4 OTH AF: 0.0719

Alfa AF: 0.0696 Hom.: 541

Bravo AF: 0.0737

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	3.9
Dann	Benign	0.86

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: rs10497711; hg19: chr2-192013921;