rs774477346
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_005045.4(RELN):c.9764-16G>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 0.00000898 in 1,447,262 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000090 ( 0 hom. )
Consequence
RELN
NM_005045.4 splice_polypyrimidine_tract, intron
NM_005045.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.59
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000898 (13/1447262) while in subpopulation SAS AF= 0.000151 (13/85890). AF 95% confidence interval is 0.0000892. There are 0 homozygotes in gnomad4_exome. There are 11 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.9764-16G>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000428762.6 | |||
SLC26A5-AS1 | NR_110141.1 | n.1366-17972C>G | intron_variant, non_coding_transcript_variant | ||||
RELN | NM_173054.3 | c.9764-16G>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.9764-16G>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_005045.4 | P5 | |||
SLC26A5-AS1 | ENST00000422488.1 | n.1366-17972C>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249470Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135056
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GnomAD4 exome AF: 0.00000898 AC: 13AN: 1447262Hom.: 0 Cov.: 28 AF XY: 0.0000153 AC XY: 11AN XY: 721026
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GnomAD4 genome ? Cov.: 32
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?
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32
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Mar 30, 2017 | - - |
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