rs74429938
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_002332.3(LRP1):c.9865+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,362,632 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00024 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00055 ( 12 hom. )
Consequence
LRP1
NM_002332.3 intron
NM_002332.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.391
Genes affected
LRP1 (HGNC:6692): (LDL receptor related protein 1) This gene encodes a member of the low-density lipoprotein receptor family of proteins. The encoded preproprotein is proteolytically processed by furin to generate 515 kDa and 85 kDa subunits that form the mature receptor (PMID: 8546712). This receptor is involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the alpha 2-macroglobulin-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer's disease patients. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000546 (661/1210336) while in subpopulation EAS AF= 0.0175 (655/37420). AF 95% confidence interval is 0.0164. There are 12 homozygotes in gnomad4_exome. There are 324 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 12 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRP1 | NM_002332.3 | c.9865+93G>A | intron_variant | ENST00000243077.8 | NP_002323.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRP1 | ENST00000243077.8 | c.9865+93G>A | intron_variant | 1 | NM_002332.3 | ENSP00000243077.3 |
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152178Hom.: 1 Cov.: 33
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GnomAD4 exome AF: 0.000546 AC: 661AN: 1210336Hom.: 12 AF XY: 0.000537 AC XY: 324AN XY: 603738
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GnomAD4 genome AF: 0.000243 AC: 37AN: 152296Hom.: 1 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74466
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ClinVar
Not reported inComputational 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