NM_007315.4:c.633+6T>A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_007315.4(STAT1):c.633+6T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,610,038 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_007315.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00325 AC: 494AN: 152218Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00307 AC: 772AN: 251186Hom.: 1 AF XY: 0.00298 AC XY: 405AN XY: 135774
GnomAD4 exome AF: 0.00447 AC: 6515AN: 1457702Hom.: 24 Cov.: 30 AF XY: 0.00440 AC XY: 3190AN XY: 725486
GnomAD4 genome AF: 0.00324 AC: 494AN: 152336Hom.: 2 Cov.: 32 AF XY: 0.00309 AC XY: 230AN XY: 74500
ClinVar
Submissions by phenotype
not provided Benign:3
STAT1: BP4, BS2 -
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Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency Uncertain:1Benign:1
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
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. -
STAT1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at