rs113229231
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_005045.4(RELN):āc.5145A>Gā(p.Ser1715=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00045 ( 0 hom., cov: 32)
Exomes š: 0.000036 ( 0 hom. )
Consequence
RELN
NM_005045.4 synonymous
NM_005045.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.564
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 7-103565343-T-C is Benign according to our data. Variant chr7-103565343-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 515710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.564 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000453 (69/152304) while in subpopulation AFR AF= 0.00166 (69/41568). AF 95% confidence interval is 0.00135. There are 0 homozygotes in gnomad4. There are 33 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.5145A>G | p.Ser1715= | synonymous_variant | 34/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.5145A>G | p.Ser1715= | synonymous_variant | 34/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.5145A>G | p.Ser1715= | synonymous_variant | 34/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000434 AC: 66AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251410Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135868
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461838Hom.: 0 Cov.: 33 AF XY: 0.0000399 AC XY: 29AN XY: 727228
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GnomAD4 genome ? AF: 0.000453 AC: 69AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33AN XY: 74466
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 10, 2020 | - - |
Computational scores
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Name
Calibrated prediction
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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