2-191090126-G-A

Variant names:

• chr2-191090126-G-A
• rs10931481
• NM_003151.4:c.274-13801C>T

Variant summary

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

The NM_003151.4(STAT4):​c.274-13801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,958 control chromosomes in the GnomAD database, including 33,400 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 0.66 (33400 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 22 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• disabling pansclerotic morphea of childhood

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.274-13801C>T		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.274-13801C>T		intron_variant	Intron 3 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100342 AN: 151842 Hom.: 33387 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.661 AC: 100389 AN: 151958 Hom.: 33400 Cov.: 31 AF XY: 0.660 AC XY: 48986 AN XY: 74276

African (AFR) AF: 0.647 AC: 26822 AN: 41436

American (AMR) AF: 0.590 AC: 9001 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2207 AN: 3460

East Asian (EAS) AF: 0.513 AC: 2660 AN: 5188

South Asian (SAS) AF: 0.631 AC: 3041 AN: 4820

European-Finnish (FIN) AF: 0.718 AC: 7558 AN: 10524

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.690 AC: 46882 AN: 67966

Other (OTH) AF: 0.662 AC: 1392 AN: 2104

Alfa AF: 0.673 Hom.: 104966

Bravo AF: 0.649

Asia WGS AF: 0.565 AC: 1962 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.87
DANN	Benign	0.37
PhyloP100		-0.22
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

Other links and lift over

dbSNP: rs10931481; hg19: chr2-191954852;