rs141976852
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_001371279.1(REEP1):c.*94T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,019,268 control chromosomes in the GnomAD database, including 506 homozygotes. 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: 𝑓 0.022 ( 69 hom., cov: 32)
Exomes 𝑓: 0.028 ( 437 hom. )
Consequence
REEP1
NM_001371279.1 3_prime_UTR
NM_001371279.1 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.36
Genes affected
REEP1 (HGNC:25786): (receptor accessory protein 1) This gene encodes a mitochondrial protein that functions to enhance the cell surface expression of odorant receptors. Mutations in this gene cause spastic paraplegia autosomal dominant type 31, a neurodegenerative disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 2-86216945-A-G is Benign according to our data. Variant chr2-86216945-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 337385.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=1, Uncertain_significance=1}. Variant chr2-86216945-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0218 (3318/152272) while in subpopulation NFE AF= 0.0336 (2286/68022). AF 95% confidence interval is 0.0325. There are 69 homozygotes in gnomad4. There are 1577 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 69 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REEP1 | NM_001371279.1 | c.*94T>C | 3_prime_UTR_variant | 9/9 | ENST00000538924.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REEP1 | ENST00000538924.7 | c.*94T>C | 3_prime_UTR_variant | 9/9 | 5 | NM_001371279.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0218 AC: 3318AN: 152154Hom.: 69 Cov.: 32
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GnomAD4 exome AF: 0.0278 AC: 24094AN: 866996Hom.: 437 Cov.: 12 AF XY: 0.0270 AC XY: 12115AN XY: 448970
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GnomAD4 genome ? AF: 0.0218 AC: 3318AN: 152272Hom.: 69 Cov.: 32 AF XY: 0.0212 AC XY: 1577AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 11, 2017 | - - |
Hereditary spastic paraplegia 31 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 02, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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