2-191145863-T-C

Variant names:

• chr2-191145863-T-C
• rs7561832
• NM_003151.4:c.273+750A>G

Variant summary

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

The NM_003151.4(STAT4):​c.273+750A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,968 control chromosomes in the GnomAD database, including 32,909 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 0.64 (32909 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 4 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

ENSG00000300654 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.273+750A>G		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.273+750A>G		intron_variant	Intron 3 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97294 AN: 151850 Hom.: 32901 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.641 AC: 97338 AN: 151968 Hom.: 32909 Cov.: 31 AF XY: 0.648 AC XY: 48144 AN XY: 74276

African (AFR) AF: 0.403 AC: 16696 AN: 41428

American (AMR) AF: 0.711 AC: 10850 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2395 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3277 AN: 5168

South Asian (SAS) AF: 0.776 AC: 3738 AN: 4816

European-Finnish (FIN) AF: 0.787 AC: 8320 AN: 10568

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.732 AC: 49764 AN: 67938

Other (OTH) AF: 0.632 AC: 1334 AN: 2110

Alfa AF: 0.682 Hom.: 4775

Bravo AF: 0.622

Asia WGS AF: 0.676 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6
DANN	Benign	0.42
PhyloP100		0.39
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: rs7561832; hg19: chr2-192010589;