chr2-191136193-C-A

Variant names:

• chr2-191136193-C-A
• rs7566274
• NM_003151.4:c.273+10420G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003151.4(STAT4):​c.273+10420G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,896 control chromosomes in the GnomAD database, including 26,321 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 0.58 (26321 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.273+10420G>T		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+10420G>T		intron_variant	Intron 3 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88425 AN: 151778 Hom.: 26302 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.582 AC: 88469 AN: 151896 Hom.: 26321 Cov.: 31 AF XY: 0.587 AC XY: 43570 AN XY: 74250

African (AFR) AF: 0.471 AC: 19483 AN: 41392

American (AMR) AF: 0.654 AC: 9982 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2423 AN: 5152

South Asian (SAS) AF: 0.621 AC: 2994 AN: 4818

European-Finnish (FIN) AF: 0.700 AC: 7380 AN: 10540

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42162 AN: 67940

Other (OTH) AF: 0.564 AC: 1191 AN: 2110

Alfa AF: 0.613 Hom.: 3634

Bravo AF: 0.573

Asia WGS AF: 0.549 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.1
DANN	Benign	0.93
PhyloP100		-0.77
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: rs7566274; hg19: chr2-192000919;