rs1400654

Positions:

• chr2-191050947-T-A
• chr2-191050947-T-G

Variant summary

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

The NM_003151.4(STAT4):​c.1251+3543A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,186 control chromosomes in the GnomAD database, including 51,008 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 0.78 (51008 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT4	NM_003151.4	c.1251+3543A>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.1251+3543A>T		intron_variant		1	NM_003151.4	ENSP00000376134	P1
STAT4	ENST00000358470.8	c.1251+3543A>T		intron_variant		1		ENSP00000351255	P1
	ENST00000658263.1	n.1300+4190T>A		intron_variant, non_coding_transcript_variant
STAT4	ENST00000495849.5	n.1319+3543A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118628 AN: 152068 Hom.: 50994 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.780 AC: 118660 AN: 152186 Hom.: 51008 Cov.: 32 AF XY: 0.786 AC XY: 58463 AN XY: 74426

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.959

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.825

Alfa AF: 0.851 Hom.: 7247

Bravo AF: 0.756

Asia WGS AF: 0.883 AC: 3073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.46

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: rs1400654; hg19: chr2-191915673;