chr2-191154646-T-G

Variant names:

• chr2-191154646-T-G
• rs16833437
• ENST00000714287.1:c.174-6442A>C

Variant summary

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

The ENST00000714287.1(STAT4):​c.174-6442A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 150,350 control chromosomes in the GnomAD database, including 23,114 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 0.52 (23113 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: STAT4 ENST00000714287.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 8 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

ENSG00000280083 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714287.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT4	ENST00000714287.1		c.174-6442A>C		intron	N/A	ENSP00000519567.1
	ENSG00000280083	ENST00000623836.1	TSL:6	n.1425A>C		non_coding_transcript_exon	Exon 1 of 1
	STAT4	ENST00000714286.1		n.174-6442A>C		intron	N/A	ENSP00000519566.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 77763 AN: 150234 Hom.: 23113 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.517 AC: 77775 AN: 150346 Hom.: 23113 Cov.: 32 AF XY: 0.525 AC XY: 38547 AN XY: 73470

African (AFR) AF: 0.210 AC: 8688 AN: 41402

American (AMR) AF: 0.641 AC: 9717 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2213 AN: 3452

East Asian (EAS) AF: 0.422 AC: 2180 AN: 5164

South Asian (SAS) AF: 0.690 AC: 3220 AN: 4664

European-Finnish (FIN) AF: 0.652 AC: 6695 AN: 10272

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43098 AN: 66944

Other (OTH) AF: 0.523 AC: 1095 AN: 2094

Alfa AF: 0.574 Hom.: 9125

Bravo AF: 0.499

Asia WGS AF: 0.528 AC: 1832 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs16833437; hg19: chr2-192019372;