ENST00000714287.1:c.173+7401T>C

Variant names:

• chr2-191160178-A-G
• rs13001658
• ENST00000714287.1:c.173+7401T>C

Variant summary

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

The ENST00000714287.1(STAT4):​c.173+7401T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,072 control chromosomes in the GnomAD database, including 31,301 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 0.63 (31301 hom., cov: 33)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.724 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.173+7401T>C		intron_variant	Intron 2 of 24			ENSP00000519567.1
STAT4	ENST00000714286.1	n.173+7401T>C		intron_variant	Intron 2 of 25			ENSP00000519566.1
STAT4	ENST00000714288.1	n.1017-4800T>C		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95749 AN: 151954 Hom.: 31285 Cov.: 33

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.630 AC: 95816 AN: 152072 Hom.: 31301 Cov.: 33 AF XY: 0.635 AC XY: 47181 AN XY: 74316

African (AFR) AF: 0.442 AC: 18329 AN: 41450

American (AMR) AF: 0.697 AC: 10668 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3095 AN: 5178

South Asian (SAS) AF: 0.745 AC: 3592 AN: 4824

European-Finnish (FIN) AF: 0.683 AC: 7199 AN: 10546

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48339 AN: 67994

Other (OTH) AF: 0.623 AC: 1314 AN: 2110

Alfa AF: 0.682 Hom.: 135849

Bravo AF: 0.620

Asia WGS AF: 0.645 AC: 2239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.78
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs13001658; hg19: chr2-192024904;