NM_003151.4:c.631-606A>T

Variant names:

• chr2-191065564-T-A
• rs3024847
• NM_003151.4:c.631-606A>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.631-606A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,048 control chromosomes in the GnomAD database, including 18,731 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 0.45 (18731 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638
• Publications: 7 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

ENSG00000288064 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.631-606A>T		intron_variant	Intron 7 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.631-606A>T		intron_variant	Intron 7 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68165 AN: 151930 Hom.: 18731 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.448 AC: 68153 AN: 152048 Hom.: 18731 Cov.: 32 AF XY: 0.452 AC XY: 33592 AN XY: 74340

African (AFR) AF: 0.121 AC: 5021 AN: 41514

American (AMR) AF: 0.431 AC: 6576 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2717 AN: 5174

South Asian (SAS) AF: 0.600 AC: 2895 AN: 4822

European-Finnish (FIN) AF: 0.623 AC: 6583 AN: 10566

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.603 AC: 40942 AN: 67942

Other (OTH) AF: 0.461 AC: 973 AN: 2110

Alfa AF: 0.520 Hom.: 2894

Bravo AF: 0.416

Asia WGS AF: 0.505 AC: 1747 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.19
PhyloP100		0.64
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: rs3024847; hg19: chr2-191930290;