chr2-191154820-C-A

Variant names:

• chr2-191154820-C-A
• rs7561569
• ENST00000623836.1:n.1251G>T

Variant summary

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

The ENST00000623836.1(ENSG00000280083):​n.1251G>T 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 0.514 in 150,134 control chromosomes in the GnomAD database, including 23,069 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 0.51 (23067 hom., cov: 33)
  • Exomes 𝑓: 0.36 (2 hom.)
• Consequence: ENSG00000280083 ENST00000623836.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 3 publications found

Genes affected

ENSG00000280083 (HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 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
ENSG00000280083	ENST00000623836.1	n.1251G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
STAT4	ENST00000714287.1	c.174-6616G>T		intron_variant	Intron 2 of 24			ENSP00000519567.1
STAT4	ENST00000714286.1	n.174-6616G>T		intron_variant	Intron 2 of 25			ENSP00000519566.1
STAT4	ENST00000714288.1	n.1178-185G>T		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.514 AC: 77089 AN: 149994 Hom.: 23067 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.357 AC: 10 AN: 28 Hom.: 2 Cov.: 0 AF XY: 0.385 AC XY: 10 AN XY: 26

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 8 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.514 AC: 77100 AN: 150106 Hom.: 23067 Cov.: 33 AF XY: 0.521 AC XY: 38189 AN XY: 73350

African (AFR) AF: 0.206 AC: 8524 AN: 41440

American (AMR) AF: 0.639 AC: 9708 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2205 AN: 3444

East Asian (EAS) AF: 0.421 AC: 2178 AN: 5172

South Asian (SAS) AF: 0.685 AC: 3182 AN: 4642

European-Finnish (FIN) AF: 0.644 AC: 6602 AN: 10252

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.641 AC: 42738 AN: 66678

Other (OTH) AF: 0.523 AC: 1096 AN: 2094

Alfa AF: 0.538 Hom.: 3596

Bravo AF: 0.497

Asia WGS AF: 0.525 AC: 1821 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.71
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs7561569; hg19: chr2-192019546;