2-191040412-C-T

Variant names:

• chr2-191040412-C-T
• rs3024873
• NM_003151.4:c.1335+653G>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.1335+653G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 152,250 control chromosomes in the GnomAD database, including 71,732 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 0.97 (71732 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• 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 (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.1335+653G>A		intron_variant	Intron 15 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.1335+653G>A		intron_variant	Intron 15 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147525 AN: 152132 Hom.: 71689 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.989

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.978

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

GnomAD4 genome AF: 0.970 AC: 147627 AN: 152250 Hom.: 71732 Cov.: 31 AF XY: 0.971 AC XY: 72244 AN XY: 74424

African (AFR) AF: 0.895 AC: 37175 AN: 41514

American (AMR) AF: 0.989 AC: 15127 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 3452 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10606 AN: 10606

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67995 AN: 68036

Other (OTH) AF: 0.978 AC: 2065 AN: 2112

Alfa AF: 0.984 Hom.: 18120

Bravo AF: 0.966

Asia WGS AF: 0.995 AC: 3460 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.19
DANN	Benign	0.25
PhyloP100		-0.69
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: rs3024873; hg19: chr2-191905138;