rs150387973
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_005045.4(RELN):c.9321C>T(p.Leu3107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,614,054 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
RELN
NM_005045.4 synonymous
NM_005045.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.504
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
Variant 7-103495771-G-A is Benign according to our data. Variant chr7-103495771-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 198004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.504 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00203 (309/152260) while in subpopulation AFR AF= 0.00722 (300/41544). AF 95% confidence interval is 0.00655. There are 1 homozygotes in gnomad4. There are 140 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.9321C>T | p.Leu3107= | synonymous_variant | 57/65 | ENST00000428762.6 | |
SLC26A5-AS1 | NR_110141.1 | n.1366-8633G>A | intron_variant, non_coding_transcript_variant | ||||
RELN | NM_173054.3 | c.9321C>T | p.Leu3107= | synonymous_variant | 57/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.9321C>T | p.Leu3107= | synonymous_variant | 57/65 | 5 | NM_005045.4 | P5 | |
SLC26A5-AS1 | ENST00000422488.1 | n.1366-8633G>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00203 AC: 309AN: 152142Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000629 AC: 158AN: 251334Hom.: 0 AF XY: 0.000398 AC XY: 54AN XY: 135838
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GnomAD4 exome AF: 0.000200 AC: 292AN: 1461794Hom.: 0 Cov.: 32 AF XY: 0.000149 AC XY: 108AN XY: 727200
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | RELN: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 23, 2015 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Norman-Roberts syndrome Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
RELN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 25, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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