7-103661529-TA-TAA
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_005045.4(RELN):c.1290-3_1290-2insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,585,310 control chromosomes in the GnomAD database, including 78 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 46 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 32 hom. )
Consequence
RELN
NM_005045.4 splice_region, splice_polypyrimidine_tract, intron
NM_005045.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.140
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 -16 ACMG points.
BP6
?
Variant 7-103661529-T-TA is Benign according to our data. Variant chr7-103661529-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 95210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2143/150122) while in subpopulation AFR AF= 0.0488 (2001/41008). AF 95% confidence interval is 0.047. There are 46 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 45 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.1290-3_1290-2insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000428762.6 | |||
RELN | NM_173054.3 | c.1290-3_1290-2insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.1290-3_1290-2insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.0142 AC: 2132AN: 150010Hom.: 45 Cov.: 32
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GnomAD3 exomes AF: 0.00415 AC: 921AN: 222016Hom.: 12 AF XY: 0.00287 AC XY: 345AN XY: 120308
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GnomAD4 exome AF: 0.00172 AC: 2462AN: 1435188Hom.: 32 Cov.: 32 AF XY: 0.00146 AC XY: 1041AN XY: 714686
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GnomAD4 genome ? AF: 0.0143 AC: 2143AN: 150122Hom.: 46 Cov.: 32 AF XY: 0.0134 AC XY: 983AN XY: 73302
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 01, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 29, 2017 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Eurofins Ntd Llc (ga) | Jan 17, 2014 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Lissencephaly, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at