chr2-191075725-G-A

Position:

• chr2-191075725-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.372+502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,054 control chromosomes in the GnomAD database, including 38,958 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 0.67 (38958 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.372+502C>T		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.372+502C>T		intron_variant		1	NM_003151.4	P1
STAT4	ENST00000358470.8	c.372+502C>T		intron_variant		1		P1
STAT4	ENST00000647167.1	c.372+502C>T		intron_variant, NMD_transcript_variant
STAT4	ENST00000495849.5	n.440+502C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101531 AN: 151938 Hom.: 38944 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.668 AC: 101546 AN: 152054 Hom.: 38958 Cov.: 31 AF XY: 0.677 AC XY: 50354 AN XY: 74340

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.696

Alfa AF: 0.799 Hom.: 112163

Bravo AF: 0.635

Asia WGS AF: 0.826 AC: 2871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.40

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: rs7601754; hg19: chr2-191940451;