rs199824078
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_030930.4(UNC93B1):c.1453G>A(p.Val485Met) variant causes a missense change. The variant allele was found at a frequency of 0.00273 in 1,258,826 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 17 hom. )
Consequence
UNC93B1
NM_030930.4 missense
NM_030930.4 missense
Scores
10
6
Clinical Significance
Conservation
PhyloP100: 4.64
Genes affected
UNC93B1 (HGNC:13481): (unc-93 homolog B1, TLR signaling regulator) This gene encodes a protein that is involved in innate and adaptive immune response by regulating toll-like receptor signaling. The encoded protein traffics nucleotide sensing toll-like receptors to the endolysosome from the endoplasmic reticulum. Deficiency of the encoded protein has been associated with herpes simplex encephalitis. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013433933).
BP6
?
Variant 11-67993705-C-T is Benign according to our data. Variant chr11-67993705-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 470491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67993705-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00275 (3043/1106496) while in subpopulation MID AF= 0.0287 (101/3522). AF 95% confidence interval is 0.0241. There are 17 homozygotes in gnomad4_exome. There are 1656 alleles in male gnomad4_exome subpopulation. Median coverage is 15. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UNC93B1 | NM_030930.4 | c.1453G>A | p.Val485Met | missense_variant | 10/11 | ENST00000227471.7 | |
UNC93B1 | XM_011545290.1 | c.1042G>A | p.Val348Met | missense_variant | 8/9 | ||
UNC93B1 | XM_011545291.3 | c.898G>A | p.Val300Met | missense_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UNC93B1 | ENST00000227471.7 | c.1453G>A | p.Val485Met | missense_variant | 10/11 | 1 | NM_030930.4 | P1 | |
UNC93B1 | ENST00000525368.1 | n.460G>A | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00260 AC: 396AN: 152212Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00422 AC: 600AN: 142166Hom.: 4 AF XY: 0.00456 AC XY: 347AN XY: 76140
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GnomAD4 exome AF: 0.00275 AC: 3043AN: 1106496Hom.: 17 Cov.: 15 AF XY: 0.00297 AC XY: 1656AN XY: 558282
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GnomAD4 genome ? AF: 0.00261 AC: 397AN: 152330Hom.: 1 Cov.: 33 AF XY: 0.00283 AC XY: 211AN XY: 74496
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | UNC93B1: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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