rs6715106

chr2-191048308-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.1251+6182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0622 in 152,270 control chromosomes in the GnomAD database, including 343 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 0.062 (343 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.1251+6182T>C		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.1251+6182T>C		intron_variant		1	NM_003151.4	P1
STAT4	ENST00000358470.8	c.1251+6182T>C		intron_variant		1		P1
	ENST00000658263.1	n.1300+1551A>G		intron_variant, non_coding_transcript_variant
STAT4	ENST00000495849.5	n.1319+6182T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9477 AN: 152152 Hom.: 343 Cov.: 31

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0622 AC: 9478 AN: 152270 Hom.: 343 Cov.: 31 AF XY: 0.0627 AC XY: 4665 AN XY: 74460

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.0552

Gnomad4 OTH AF: 0.0730

Alfa AF: 0.0557 Hom.: 73

Bravo AF: 0.0633

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.3
Dann	Benign	0.68

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: rs6715106; hg19: chr2-191913034;