rs1461905374
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015627.3(LDLRAP1):c.459+2T>G variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_015627.3 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LDLRAP1 | NM_015627.3 | c.459+2T>G | splice_donor_variant, intron_variant | ENST00000374338.5 | NP_056442.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LDLRAP1 | ENST00000374338.5 | c.459+2T>G | splice_donor_variant, intron_variant | 1 | NM_015627.3 | ENSP00000363458.4 | ||||
LDLRAP1 | ENST00000462394.1 | n.209T>G | non_coding_transcript_exon_variant | 2/2 | 2 | |||||
LDLRAP1 | ENST00000488127.1 | n.929+2T>G | splice_donor_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250996Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135680
GnomAD4 exome AF: 0.00000215 AC: 3AN: 1397040Hom.: 0 Cov.: 30 AF XY: 0.00000286 AC XY: 2AN XY: 698112
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Dec 27, 2021 | - - |
Hypercholesterolemia, familial, 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2005 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at