chr7-103500731-GGCTTT-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS1
The NM_005045.4(RELN):c.8667+9_8667+13del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000676 in 1,613,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
RELN
NM_005045.4 intron
NM_005045.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.127
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.
BP6
Variant 7-103500731-GGCTTT-G is Benign according to our data. Variant chr7-103500731-GGCTTT-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436520.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000789 (12/152170) while in subpopulation AMR AF= 0.000327 (5/15272). AF 95% confidence interval is 0.000129. There are 0 homozygotes in gnomad4. There are 8 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.8667+9_8667+13del | intron_variant | ENST00000428762.6 | |||
SLC26A5-AS1 | NR_110141.1 | n.1366-3672_1366-3668del | intron_variant, non_coding_transcript_variant | ||||
RELN | NM_173054.3 | c.8667+9_8667+13del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.8667+9_8667+13del | intron_variant | 5 | NM_005045.4 | P5 | |||
SLC26A5-AS1 | ENST00000422488.1 | n.1366-3672_1366-3668del | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251072Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135758
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GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461262Hom.: 0 AF XY: 0.0000839 AC XY: 61AN XY: 726962
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GnomAD4 genome AF: 0.0000789 AC: 12AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74340
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 13, 2016 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
RELN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 27, 2024 | This variant is classified as likely 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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Find out detailed SpliceAI scores and Pangolin per-transcript scores at