chr2-191170317-T-C

Variant names:

• chr2-191170317-T-C
• rs10176621
• ENST00000714287.1:c.26+2267A>G

Variant summary

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

The ENST00000714287.1(STAT4):​c.26+2267A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,990 control chromosomes in the GnomAD database, including 15,843 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 0.39 (15843 hom., cov: 32)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000714287.1	c.26+2267A>G		intron_variant	Intron 1 of 24			ENSP00000519567.1
STAT4	ENST00000714286.1	n.26+2267A>G		intron_variant	Intron 1 of 25			ENSP00000519566.1
STAT4	ENST00000714288.1	n.748-1681A>G		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59700 AN: 151872 Hom.: 15791 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.394 AC: 59814 AN: 151990 Hom.: 15843 Cov.: 32 AF XY: 0.386 AC XY: 28699 AN XY: 74288

African (AFR) AF: 0.763 AC: 31649 AN: 41456

American (AMR) AF: 0.270 AC: 4124 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2075 AN: 5164

South Asian (SAS) AF: 0.239 AC: 1155 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2451 AN: 10574

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16410 AN: 67930

Other (OTH) AF: 0.372 AC: 783 AN: 2106

Alfa AF: 0.322 Hom.: 1357

Bravo AF: 0.415

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.64
PhyloP100		-0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10176621; hg19: chr2-192035043;