rs7595886

Variant names:

• chr2-191174012-C-T
• rs7595886
• ENST00000714288.1:n.482G>A

Variant summary

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

The ENST00000714288.1(STAT4):​n.482G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,106 control chromosomes in the GnomAD database, including 7,348 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 0.25 (7348 hom., cov: 32)
• Consequence: STAT4 ENST00000714288.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 4 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]

HMGB1P27 (HGNC:39118): (high mobility group box 1 pseudogene 27)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 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	ENST00000714288.1	n.482G>A		non_coding_transcript_exon_variant	Exon 2 of 7
STAT4	ENST00000714335.1	n.714G>A		non_coding_transcript_exon_variant	Exon 4 of 4
HMGB1P27	ENST00000431429.1	n.-221C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37491 AN: 151988 Hom.: 7319 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.247 AC: 37577 AN: 152106 Hom.: 7348 Cov.: 32 AF XY: 0.239 AC XY: 17793 AN XY: 74358

African (AFR) AF: 0.539 AC: 22337 AN: 41436

American (AMR) AF: 0.152 AC: 2321 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1808 AN: 5178

South Asian (SAS) AF: 0.200 AC: 966 AN: 4822

European-Finnish (FIN) AF: 0.0643 AC: 682 AN: 10606

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8422 AN: 67992

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.167 Hom.: 12007

Bravo AF: 0.268

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.63
DANN	Benign	0.51
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs7595886; hg19: chr2-192038738;