rs41509946
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_007315.4(STAT1):c.990G>A(p.Gln330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,614,146 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 21 hom. )
Consequence
STAT1
NM_007315.4 synonymous
NM_007315.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.28
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
?
Variant 2-190991275-C-T is Benign according to our data. Variant chr2-190991275-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 333284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-190991275-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=3.28 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00313 (476/152278) while in subpopulation SAS AF= 0.0104 (50/4818). AF 95% confidence interval is 0.00809. There are 1 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 21 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAT1 | NM_007315.4 | c.990G>A | p.Gln330= | synonymous_variant | 11/25 | ENST00000361099.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAT1 | ENST00000361099.8 | c.990G>A | p.Gln330= | synonymous_variant | 11/25 | 1 | NM_007315.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00313 AC: 476AN: 152160Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00350 AC: 881AN: 251462Hom.: 6 AF XY: 0.00400 AC XY: 544AN XY: 135902
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GnomAD4 exome AF: 0.00353 AC: 5164AN: 1461868Hom.: 21 Cov.: 31 AF XY: 0.00381 AC XY: 2768AN XY: 727234
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GnomAD4 genome ? AF: 0.00313 AC: 476AN: 152278Hom.: 1 Cov.: 32 AF XY: 0.00336 AC XY: 250AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | STAT1: BP4, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2016 | - - |
Immunodeficiency 31B;C3279990:Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome;C4013950:Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at