rs149473868
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP2PP3BS1_Supporting
The NM_005045.4(RELN):c.5969C>T(p.Pro1990Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000291 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005045.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.5969C>T | p.Pro1990Leu | missense_variant, splice_region_variant | 39/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.5969C>T | p.Pro1990Leu | missense_variant, splice_region_variant | 39/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.5969C>T | p.Pro1990Leu | missense_variant, splice_region_variant | 39/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 151990Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000598 AC: 15AN: 250962Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135644
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461564Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727088
GnomAD4 genome AF: 0.000118 AC: 18AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74322
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 2017 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1990 of the RELN protein (p.Pro1990Leu). This variant is present in population databases (rs149473868, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with RELN-related conditions. ClinVar contains an entry for this variant (Variation ID: 429549). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 01, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 33004838) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at