rs777827146
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_015627.3(LDLRAP1):c.906G>A(p.Gln302=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,390 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
LDLRAP1
NM_015627.3 synonymous
NM_015627.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0450
Genes affected
LDLRAP1 (HGNC:18640): (low density lipoprotein receptor adaptor protein 1) The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 1-25566971-G-A is Benign according to our data. Variant chr1-25566971-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 468291.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.045 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLRAP1 | NM_015627.3 | c.906G>A | p.Gln302= | synonymous_variant | 9/9 | ENST00000374338.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLRAP1 | ENST00000374338.5 | c.906G>A | p.Gln302= | synonymous_variant | 9/9 | 1 | NM_015627.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250138Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135644
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461166Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726910
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypercholesterolemia, familial, 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2021 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at