rs114190729
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BS1_Supporting
The NM_005045.4(RELN):c.5711C>T(p.Thr1904Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,613,258 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. T1904K) 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.5711C>T | p.Thr1904Met | missense_variant | 38/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.5711C>T | p.Thr1904Met | missense_variant | 38/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.5711C>T | p.Thr1904Met | missense_variant | 38/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000375 AC: 57AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000294 AC: 74AN: 251376Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135870
GnomAD4 exome AF: 0.000524 AC: 765AN: 1460970Hom.: 0 Cov.: 31 AF XY: 0.000526 AC XY: 382AN XY: 726842
GnomAD4 genome ? AF: 0.000374 AC: 57AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29AN XY: 74458
ClinVar
Submissions by phenotype
Norman-Roberts syndrome Uncertain:2
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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 08, 2020 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 31, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 26, 2023 | PP3 - |
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 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2021 | Unlikely to be causative of RELN-related lateral temporal epilepsy (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at