2-191119560-A-T

Position:

• chr2-191119560-A-T

Variant summary

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

The NM_003151.4(STAT4):​c.273+27053T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,018 control chromosomes in the GnomAD database, including 29,278 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 0.61 (29278 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.273+27053T>A		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.273+27053T>A		intron_variant		1	NM_003151.4	P1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93145 AN: 151900 Hom.: 29242 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.613 AC: 93227 AN: 152018 Hom.: 29278 Cov.: 31 AF XY: 0.622 AC XY: 46252 AN XY: 74308

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.610

Alfa AF: 0.629 Hom.: 3809

Bravo AF: 0.604

Asia WGS AF: 0.781 AC: 2709 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.32

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: rs4341967; hg19: chr2-191984286;