rs2229864
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005045.4(RELN):āc.8046T>Cā(p.His2682=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,780 control chromosomes in the GnomAD database, including 143,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.50 ( 21989 hom., cov: 32)
Exomes š: 0.39 ( 121938 hom. )
Consequence
RELN
NM_005045.4 synonymous
NM_005045.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.43
Genes affected
RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 7-103515258-A-G is Benign according to our data. Variant chr7-103515258-A-G is described in ClinVar as [Benign]. Clinvar id is 95230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103515258-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.43 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.8046T>C | p.His2682= | synonymous_variant | 50/65 | ENST00000428762.6 | NP_005036.2 | |
RELN | NM_173054.3 | c.8046T>C | p.His2682= | synonymous_variant | 50/64 | NP_774959.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.8046T>C | p.His2682= | synonymous_variant | 50/65 | 5 | NM_005045.4 | ENSP00000392423 | P5 |
Frequencies
GnomAD3 genomes AF: 0.504 AC: 76497AN: 151894Hom.: 21941 Cov.: 32
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GnomAD3 exomes AF: 0.463 AC: 116373AN: 251162Hom.: 30209 AF XY: 0.461 AC XY: 62563AN XY: 135758
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GnomAD4 exome AF: 0.391 AC: 571285AN: 1461768Hom.: 121938 Cov.: 55 AF XY: 0.396 AC XY: 288107AN XY: 727174
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GnomAD4 genome AF: 0.504 AC: 76615AN: 152012Hom.: 21989 Cov.: 32 AF XY: 0.507 AC XY: 37704AN XY: 74320
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 03, 2012 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Norman-Roberts syndrome Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 07, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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