2-191074461-C-T

Position:

• chr2-191074461-C-T

Variant summary

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

The NM_003151.4(STAT4):​c.373-1271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,134 control chromosomes in the GnomAD database, including 48,950 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 0.77 (48950 hom., cov: 31)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT4	NM_003151.4	c.373-1271G>A		intron_variant		ENST00000392320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT4	ENST00000392320.7	c.373-1271G>A		intron_variant		1	NM_003151.4	P1
STAT4	ENST00000358470.8	c.373-1271G>A		intron_variant		1		P1
STAT4	ENST00000647167.1	c.373-1271G>A		intron_variant, NMD_transcript_variant
STAT4	ENST00000495849.5	n.441-1271G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117536 AN: 152016 Hom.: 48939 Cov.: 31

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.773 AC: 117581 AN: 152134 Hom.: 48950 Cov.: 31 AF XY: 0.781 AC XY: 58128 AN XY: 74392

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.974

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.782

Alfa AF: 0.871 Hom.: 78600

Bravo AF: 0.747

Asia WGS AF: 0.949 AC: 3299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.60

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: rs2459611; hg19: chr2-191939187;