rs74952625
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_005045.4(RELN):c.8120-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,609,420 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 0.0017 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
RELN
NM_005045.4 splice_polypyrimidine_tract, intron
NM_005045.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0005777
2
Clinical Significance
Conservation
PhyloP100: 0.482
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.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 7-103511014-A-G is Benign according to our data. Variant chr7-103511014-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 197926.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 = 0.00168 (256/152312) while in subpopulation AFR AF= 0.00592 (246/41560). AF 95% confidence interval is 0.00531. There are 1 homozygotes in gnomad4. There are 108 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.8120-9T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000428762.6 | |||
SLC26A5-AS1 | NR_110141.1 | n.1487-1755A>G | intron_variant, non_coding_transcript_variant | ||||
RELN | NM_173054.3 | c.8120-9T>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.8120-9T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_005045.4 | P5 | |||
SLC26A5-AS1 | ENST00000422488.1 | n.1487-1755A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00169 AC: 257AN: 152194Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000561 AC: 140AN: 249430Hom.: 0 AF XY: 0.000326 AC XY: 44AN XY: 134790
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GnomAD4 exome AF: 0.000170 AC: 247AN: 1457108Hom.: 0 Cov.: 29 AF XY: 0.000143 AC XY: 104AN XY: 725068
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 14, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 31, 2015 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 24, 2021 | - - |
RELN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 10, 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
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at