2-191032814-C-T

Variant names:

• chr2-191032814-C-T
• rs925847
• NM_003151.4:c.2044+144G>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.2044+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 824,180 control chromosomes in the GnomAD database, including 37,585 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 0.32 (7967 hom., cov: 32)
  • Exomes 𝑓: 0.29 (29618 hom.)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 40 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003151.4. 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_003151.4	MANE Select	c.2044+144G>A		intron	N/A	NP_003142.1	Q14765
	STAT4	NM_001243835.2		c.2044+144G>A		intron	N/A	NP_001230764.1	Q14765

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	ENST00000392320.7	TSL:1 MANE Select	c.2044+144G>A		intron	N/A	ENSP00000376134.2	Q14765
	STAT4	ENST00000358470.8	TSL:1	c.2044+144G>A		intron	N/A	ENSP00000351255.4	Q14765
	STAT4	ENST00000450994.2	TSL:1	c.2044+144G>A		intron	N/A	ENSP00000412397.2	Q14765

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48117 AN: 151882 Hom.: 7965 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.289 AC: 194347 AN: 672180 Hom.: 29618 Cov.: 9 AF XY: 0.289 AC XY: 99194 AN XY: 343054

African (AFR) AF: 0.394 AC: 6112 AN: 15512

American (AMR) AF: 0.273 AC: 4702 AN: 17246

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 4971 AN: 14742

East Asian (EAS) AF: 0.499 AC: 15345 AN: 30748

South Asian (SAS) AF: 0.275 AC: 12634 AN: 46010

European-Finnish (FIN) AF: 0.277 AC: 9905 AN: 35818

Middle Eastern (MID) AF: 0.394 AC: 952 AN: 2414

European-Non Finnish (NFE) AF: 0.272 AC: 129612 AN: 476788

Other (OTH) AF: 0.307 AC: 10114 AN: 32902

GnomAD4 genome AF: 0.317 AC: 48137 AN: 152000 Hom.: 7967 Cov.: 32 AF XY: 0.317 AC XY: 23551 AN XY: 74312

African (AFR) AF: 0.394 AC: 16337 AN: 41412

American (AMR) AF: 0.301 AC: 4595 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2424 AN: 5162

South Asian (SAS) AF: 0.288 AC: 1388 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2939 AN: 10584

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18147 AN: 67972

Other (OTH) AF: 0.341 AC: 718 AN: 2108

Alfa AF: 0.288 Hom.: 11139

Bravo AF: 0.324

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.79
PhyloP100		-0.51
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: rs925847; hg19: chr2-191897540;