rs200428576
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BS1_Supporting
The NM_005045.4(RELN):āc.4495G>Cā(p.Asp1499His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1499G) has been classified as Uncertain significance.
Frequency
Consequence
NM_005045.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.4495G>C | p.Asp1499His | missense_variant | 30/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.4495G>C | p.Asp1499His | missense_variant | 30/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.4495G>C | p.Asp1499His | missense_variant | 30/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000127 AC: 32AN: 251408Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135870
GnomAD4 exome AF: 0.000122 AC: 178AN: 1461652Hom.: 0 Cov.: 32 AF XY: 0.000125 AC XY: 91AN XY: 727174
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74388
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 14, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2017 | A variant of uncertain significance has been identified in the RELN gene. The D1499H variant has been reported previously in an individual with autism spectrum disorder; however, no further information was provided (Matsunami et al., 2014). The D1499H variant is observed in 17/66738 (0.03%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D1499H variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7;C4551957:Epilepsy, familial temporal lobe, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Norman-Roberts syndrome Uncertain:1
Uncertain significance, 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Autism Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | May 29, 2019 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at