rs148696946
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_001199138.2(NLRC4):c.90G>A(p.Trp30*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
NLRC4
NM_001199138.2 stop_gained
NM_001199138.2 stop_gained
Scores
2
2
2
Clinical Significance
Conservation
PhyloP100: 0.688
Genes affected
NLRC4 (HGNC:16412): (NLR family CARD domain containing 4) This gene encodes a member of the caspase recruitment domain-containing NLR family. Family members play essential roles in innate immune response to a wide range of pathogenic organisms, tissue damage and other cellular stresses. Mutations in this gene result in autoinflammation with infantile enterocolitis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
Variant 2-32252591-C-T is Benign according to our data. Variant chr2-32252591-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542043.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000164 (25/152330) while in subpopulation AFR AF= 0.000577 (24/41564). AF 95% confidence interval is 0.000398. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NLRC4 | NM_001199138.2 | c.90G>A | p.Trp30* | stop_gained | 3/9 | ENST00000402280.6 | NP_001186067.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NLRC4 | ENST00000402280.6 | c.90G>A | p.Trp30* | stop_gained | 3/9 | 1 | NM_001199138.2 | ENSP00000385428.1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152212Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251468Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135900
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461818Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727216
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152330Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Periodic fever-infantile enterocolitis-autoinflammatory syndrome;C4015276:Familial cold autoinflammatory syndrome 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 09, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
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Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
Vest4
GERP RS
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