rs13426947

Positions:

• chr2-191068528-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003151.4(STAT4):​c.544+1165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,026 control chromosomes in the GnomAD database, including 3,362 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 0.20 (3362 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT4	NM_003151.4	c.544+1165C>T		intron_variant		ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.544+1165C>T		intron_variant		1	NM_003151.4	ENSP00000376134	P1
STAT4	ENST00000358470.8	c.544+1165C>T		intron_variant		1		ENSP00000351255	P1
STAT4	ENST00000647167.1	c.*35C>T		3_prime_UTR_variant, NMD_transcript_variant	7/8			ENSP00000495153
STAT4	ENST00000495849.5	n.612+1165C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30789 AN: 151906 Hom.: 3352 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.212

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.203 AC: 30822 AN: 152026 Hom.: 3362 Cov.: 32 AF XY: 0.208 AC XY: 15465 AN XY: 74312

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.217

Alfa AF: 0.228 Hom.: 862

Bravo AF: 0.206

Asia WGS AF: 0.284 AC: 987 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs13426947; hg19: chr2-191933254;