chr2-191151202-C-T

Variant names:

• chr2-191151202-C-T
• rs2278940
• ENST00000358470.8:c.-2+132G>A

Variant summary

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

The NM_001243835.2(STAT4):​c.-2+132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 985,528 control chromosomes in the GnomAD database, including 3,034 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 0.075 (474 hom., cov: 32)
  • Exomes 𝑓: 0.077 (2560 hom.)
• Consequence: STAT4 NM_001243835.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• 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):

• disabling pansclerotic morphea of childhood

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243835.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	NM_001243835.2		c.-2+132G>A		intron	N/A	NP_001230764.1	Q14765
	STAT4	NM_003151.4	MANE Select	c.-257G>A		upstream_gene	N/A	NP_003142.1	Q14765

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	ENST00000358470.8	TSL:1	c.-2+132G>A		intron	N/A	ENSP00000351255.4	Q14765
	STAT4	ENST00000450994.2	TSL:1	c.-70+132G>A		intron	N/A	ENSP00000412397.2	Q14765
	STAT4	ENST00000960213.1		c.-553G>A		5_prime_UTR	Exon 1 of 24	ENSP00000630272.1

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11440 AN: 152112 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0647

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.0768 AC: 63965 AN: 833298 Hom.: 2560 Cov.: 30 AF XY: 0.0769 AC XY: 29581 AN XY: 384872

African (AFR) AF: 0.0844 AC: 1333 AN: 15792

American (AMR) AF: 0.0436 AC: 43 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 235 AN: 5152

East Asian (EAS) AF: 0.181 AC: 657 AN: 3632

South Asian (SAS) AF: 0.0628 AC: 1034 AN: 16466

European-Finnish (FIN) AF: 0.0284 AC: 8 AN: 282

Middle Eastern (MID) AF: 0.0820 AC: 133 AN: 1622

European-Non Finnish (NFE) AF: 0.0764 AC: 58252 AN: 762052

Other (OTH) AF: 0.0831 AC: 2270 AN: 27314

GnomAD4 genome AF: 0.0752 AC: 11448 AN: 152230 Hom.: 474 Cov.: 32 AF XY: 0.0732 AC XY: 5451 AN XY: 74438

African (AFR) AF: 0.0903 AC: 3749 AN: 41528

American (AMR) AF: 0.0484 AC: 741 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3472

East Asian (EAS) AF: 0.177 AC: 915 AN: 5176

South Asian (SAS) AF: 0.0645 AC: 311 AN: 4820

European-Finnish (FIN) AF: 0.0419 AC: 445 AN: 10618

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0723 AC: 4918 AN: 68004

Other (OTH) AF: 0.0749 AC: 158 AN: 2110

Alfa AF: 0.0792 Hom.: 152

Bravo AF: 0.0767

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.81
PhyloP100		-0.10
PromoterAI		-0.022	Neutral
Mutation Taster		=300/0	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: rs2278940; hg19: chr2-192015928;