2-190968814-G-T

Variant names:

• chr2-190968814-G-T
• rs1400657
• ENST00000698141.1:c.*1889C>A

Variant summary

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

The ENST00000698141.1(STAT1):​c.*1889C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,090 control chromosomes in the GnomAD database, including 55,979 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 0.86 (55979 hom., cov: 31)
• Consequence: STAT1 ENST00000698141.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 8 publications found

Genes affected

STAT1 (HGNC:11362): (signal transducer and activator of transcription 1) The protein encoded by this gene is a member of the STAT protein family. 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. The protein encoded by this gene can be activated by various ligands including interferon-alpha, interferon-gamma, EGF, PDGF and IL6. This protein mediates the expression of a variety of genes, which is thought to be important for cell viability in response to different cell stimuli and pathogens. The protein plays an important role in immune responses to viral, fungal and mycobacterial pathogens. Mutations in this gene are associated with Immunodeficiency 31B, 31A, and 31C. [provided by RefSeq, Jun 2020]

STAT1 Gene-Disease associations (from GenCC):

• autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, Orphanet
• immunodeficiency 31B

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.892 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
STAT1	ENST00000698141.1	c.*1889C>A		3_prime_UTR_variant	Exon 26 of 26			ENSP00000513582.1
STAT1	ENST00000698142.1	c.*1889C>A		3_prime_UTR_variant	Exon 24 of 24			ENSP00000513583.1
STAT1	ENST00000673847.1	c.2238+6016C>A		intron_variant	Intron 24 of 24			ENSP00000501185.1

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130031 AN: 151972 Hom.: 55940 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.856 AC: 130126 AN: 152090 Hom.: 55979 Cov.: 31 AF XY: 0.857 AC XY: 63742 AN XY: 74360

African (AFR) AF: 0.761 AC: 31571 AN: 41476

American (AMR) AF: 0.889 AC: 13578 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2852 AN: 3468

East Asian (EAS) AF: 0.855 AC: 4433 AN: 5184

South Asian (SAS) AF: 0.823 AC: 3964 AN: 4818

European-Finnish (FIN) AF: 0.938 AC: 9946 AN: 10600

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.898 AC: 60989 AN: 67952

Other (OTH) AF: 0.829 AC: 1750 AN: 2112

Alfa AF: 0.878 Hom.: 104716

Bravo AF: 0.848

Asia WGS AF: 0.857 AC: 2982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs1400657; hg19: chr2-191833540;