rs34327883
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_018368.4(LMBRD1):c.801C>T(p.Arg267Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,524 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 32 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 39 hom. )
Consequence
LMBRD1
NM_018368.4 synonymous
NM_018368.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.16
Genes affected
LMBRD1 (HGNC:23038): (LMBR1 domain containing 1) This gene encodes a lysosomal membrane protein that may be involved in the transport and metabolism of cobalamin. This protein also interacts with the large form of the hepatitis delta antigen and may be required for the nucleocytoplasmic shuttling of the hepatitis delta virus. Mutations in this gene are associated with the vitamin B12 metabolism disorder termed, homocystinuria-megaloblastic anemia complementation type F.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 6-69713759-G-A is Benign according to our data. Variant chr6-69713759-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 357775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.16 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1572/152136) while in subpopulation AFR AF= 0.0364 (1512/41518). AF 95% confidence interval is 0.0349. There are 32 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 32 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LMBRD1 | NM_018368.4 | c.801C>T | p.Arg267Arg | synonymous_variant | 9/16 | ENST00000649934.3 | NP_060838.3 | |
LMBRD1 | NM_001363722.2 | c.582C>T | p.Arg194Arg | synonymous_variant | 9/16 | NP_001350651.1 | ||
LMBRD1 | NM_001367271.1 | c.582C>T | p.Arg194Arg | synonymous_variant | 9/16 | NP_001354200.1 | ||
LMBRD1 | NM_001367272.1 | c.582C>T | p.Arg194Arg | synonymous_variant | 9/16 | NP_001354201.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LMBRD1 | ENST00000649934.3 | c.801C>T | p.Arg267Arg | synonymous_variant | 9/16 | NM_018368.4 | ENSP00000497690.1 |
Frequencies
GnomAD3 genomes AF: 0.0103 AC: 1566AN: 152018Hom.: 32 Cov.: 32
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GnomAD3 exomes AF: 0.00299 AC: 749AN: 250920Hom.: 16 AF XY: 0.00199 AC XY: 270AN XY: 135590
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GnomAD4 exome AF: 0.00113 AC: 1647AN: 1461388Hom.: 39 Cov.: 32 AF XY: 0.000928 AC XY: 675AN XY: 727000
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GnomAD4 genome AF: 0.0103 AC: 1572AN: 152136Hom.: 32 Cov.: 32 AF XY: 0.00955 AC XY: 710AN XY: 74374
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Methylmalonic aciduria and homocystinuria type cblF Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 08, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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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