2-191093930-C-T

Variant names:

• chr2-191093930-C-T
• rs4274624
• NM_003151.4:c.274-17605G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003151.4(STAT4):​c.274-17605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,126 control chromosomes in the GnomAD database, including 46,760 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 0.78 (46760 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.274-17605G>A		intron_variant	Intron 3 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.274-17605G>A		intron_variant	Intron 3 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118819 AN: 152008 Hom.: 46723 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.782 AC: 118904 AN: 152126 Hom.: 46760 Cov.: 32 AF XY: 0.778 AC XY: 57858 AN XY: 74348

African (AFR) AF: 0.854 AC: 35418 AN: 41492

American (AMR) AF: 0.690 AC: 10547 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2618 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3326 AN: 5170

South Asian (SAS) AF: 0.714 AC: 3440 AN: 4820

European-Finnish (FIN) AF: 0.770 AC: 8141 AN: 10574

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52837 AN: 68006

Other (OTH) AF: 0.769 AC: 1626 AN: 2114

Alfa AF: 0.747 Hom.: 10047

Bravo AF: 0.778

Asia WGS AF: 0.668 AC: 2322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs4274624; hg19: chr2-191958656;