6-69676170-G-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_018368.4(LMBRD1):āc.1611C>Gā(p.Val537=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
LMBRD1
NM_018368.4 synonymous
NM_018368.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.742
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 6-69676170-G-C is Benign according to our data. Variant chr6-69676170-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 910062.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.742 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LMBRD1 | NM_018368.4 | c.1611C>G | p.Val537= | synonymous_variant | 16/16 | ENST00000649934.3 | NP_060838.3 | |
| LMBRD1 | NM_001363722.2 | c.1392C>G | p.Val464= | synonymous_variant | 16/16 | NP_001350651.1 | ||
| LMBRD1 | NM_001367271.1 | c.1392C>G | p.Val464= | synonymous_variant | 16/16 | NP_001354200.1 | ||
| LMBRD1 | NM_001367272.1 | c.1392C>G | p.Val464= | synonymous_variant | 16/16 | NP_001354201.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| LMBRD1 | ENST00000649934.3 | c.1611C>G | p.Val537= | synonymous_variant | 16/16 | NM_018368.4 | ENSP00000497690 | P2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250766Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135512
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460366Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726534
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GnomAD4 genome 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74424
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Methylmalonic aciduria and homocystinuria type cblF Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 28, 2023 | - - |
| Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this 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