rs3024866

Variant names:

• chr2-191058115-G-A
• rs3024866
• NM_003151.4:c.1113-4C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-191058115-G-A
• chr2-191058115-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003151.4(STAT4):​c.1113-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,613,274 control chromosomes in the GnomAD database, including 406,290 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (28572 hom., cov: 31)
  • Exomes 𝑓: 0.71 (377718 hom.)
• Consequence: STAT4 NM_003151.4 splice_region, intron
• Scores: Splicing: ADA: 0.0006460
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0620
• Publications: 37 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):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• disabling pansclerotic morphea of childhood

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000288064 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 2-191058115-G-A is Benign according to our data. Variant chr2-191058115-G-A is described in ClinVar as Benign. ClinVar VariationId is 403495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT4	NM_003151.4	c.1113-4C>T		splice_region_variant, intron_variant	Intron 12 of 23	ENST00000392320.7	NP_003142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.1113-4C>T		splice_region_variant, intron_variant	Intron 12 of 23	1	NM_003151.4	ENSP00000376134.2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86371 AN: 151806 Hom.: 28577 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.602

GnomAD2 exomes AF: 0.642 AC: 160976 AN: 250916 AF XY: 0.657

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.665

Gnomad EAS exome AF: 0.517

Gnomad FIN exome AF: 0.692

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.667

GnomAD4 exome AF: 0.712 AC: 1040434 AN: 1461350 Hom.: 377718 Cov.: 42 AF XY: 0.712 AC XY: 517871 AN XY: 727016

African (AFR) AF: 0.198 AC: 6638 AN: 33472

American (AMR) AF: 0.517 AC: 23104 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 17475 AN: 26128

East Asian (EAS) AF: 0.556 AC: 22030 AN: 39650

South Asian (SAS) AF: 0.659 AC: 56831 AN: 86246

European-Finnish (FIN) AF: 0.694 AC: 37054 AN: 53412

Middle Eastern (MID) AF: 0.621 AC: 3581 AN: 5766

European-Non Finnish (NFE) AF: 0.749 AC: 832861 AN: 1111586

Other (OTH) AF: 0.677 AC: 40860 AN: 60376

GnomAD4 genome AF: 0.569 AC: 86369 AN: 151924 Hom.: 28572 Cov.: 31 AF XY: 0.568 AC XY: 42203 AN XY: 74244

African (AFR) AF: 0.219 AC: 9073 AN: 41374

American (AMR) AF: 0.553 AC: 8435 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2382 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2745 AN: 5182

South Asian (SAS) AF: 0.675 AC: 3257 AN: 4822

European-Finnish (FIN) AF: 0.700 AC: 7379 AN: 10538

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50913 AN: 67966

Other (OTH) AF: 0.600 AC: 1264 AN: 2106

Alfa AF: 0.683 Hom.: 55817

Bravo AF: 0.540

Asia WGS AF: 0.559 AC: 1945 AN: 3478

EpiCase AF: 0.740

EpiControl AF: 0.737

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.7
DANN	Benign	0.78
PhyloP100		-0.062
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00065
dbscSNV1_RF	Benign	0.060
SpliceAI score (max)		0.030		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: rs3024866; hg19: chr2-191922841; COSMIC: COSV61831638;