chr2-191105604-C-G

Variant names:

• chr2-191105604-C-G
• rs13401064
• NM_003151.4:c.274-29279G>C

Variant summary

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

The NM_003151.4(STAT4):​c.274-29279G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0856 in 152,062 control chromosomes in the GnomAD database, including 601 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 0.086 (601 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.274-29279G>C		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.274-29279G>C		intron_variant	Intron 3 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13010 AN: 151944 Hom.: 600 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.0819

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

GnomAD4 genome AF: 0.0856 AC: 13016 AN: 152062 Hom.: 601 Cov.: 32 AF XY: 0.0840 AC XY: 6244 AN XY: 74330

African (AFR) AF: 0.101 AC: 4193 AN: 41466

American (AMR) AF: 0.0675 AC: 1031 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3470

East Asian (EAS) AF: 0.0958 AC: 497 AN: 5186

South Asian (SAS) AF: 0.130 AC: 628 AN: 4816

European-Finnish (FIN) AF: 0.0511 AC: 539 AN: 10558

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0823 AC: 5594 AN: 67974

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0817 Hom.: 66

Bravo AF: 0.0873

Asia WGS AF: 0.0990 AC: 344 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.44
PhyloP100		-0.27
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: rs13401064; hg19: chr2-191970330;