rs12467660

Variant names:

• chr2-191166924-A-C
• rs12467660
• ENST00000714287.1:c.173+655T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-191166924-A-C
• chr2-191166924-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000714287.1(STAT4):​c.173+655T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,146 control chromosomes in the GnomAD database, including 47,604 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 (47604 hom., cov: 31)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000714287.1	c.173+655T>G		intron_variant	Intron 2 of 24			ENSP00000519567.1
STAT4	ENST00000714286.1	n.173+655T>G		intron_variant	Intron 2 of 25			ENSP00000519566.1
STAT4	ENST00000714288.1	n.1016+655T>G		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117671 AN: 152028 Hom.: 47584 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.774 AC: 117733 AN: 152146 Hom.: 47604 Cov.: 31 AF XY: 0.781 AC XY: 58151 AN XY: 74422

African (AFR) AF: 0.520 AC: 21535 AN: 41436

American (AMR) AF: 0.858 AC: 13118 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3245 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3365 AN: 5174

South Asian (SAS) AF: 0.821 AC: 3960 AN: 4824

European-Finnish (FIN) AF: 0.937 AC: 9945 AN: 10614

Middle Eastern (MID) AF: 0.856 AC: 250 AN: 292

European-Non Finnish (NFE) AF: 0.881 AC: 59905 AN: 68028

Other (OTH) AF: 0.789 AC: 1666 AN: 2112

Alfa AF: 0.814 Hom.: 9928

Bravo AF: 0.755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.59
PhyloP100		0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12467660; hg19: chr2-192031650;