rs587779752
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_022458.4(LMBR1):c.423+4915C>T variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,136 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 Pathogenic (★).
Frequency
Consequence
NM_022458.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 32
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Tibia, hypoplasia or aplasia of, with polydactyly Pathogenic:2
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Triphalangeal thumb Pathogenic:1
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not provided Pathogenic:1
This sequence change falls in intron 5 of the LMBR1 gene. It does not directly change the encoded amino acid sequence of the LMBR1 protein. This variant is present in population databases (rs587779752, gnomAD 0.1%). This variant has been observed in individual(s) with preaxial polydactyly and/or triphalangeal thumb (PMID: 24777739). It has also been observed to segregate with disease in related individuals. This variant is also known as ZRS 402C>T. ClinVar contains an entry for this variant (Variation ID: 126371). Studies have shown that this variant affects the ZPA regulatory sequence (ZRS) within intron 5 of the LMBR1 gene, which regulates the expression of certain genes that are important for limb development (PMID: 29651423). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. For these reasons, this variant has been classified as Pathogenic. -
Polydactyly of a triphalangeal thumb Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at