rs362793
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_005045.4(RELN):āc.5880A>Gā(p.Thr1960=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,614,014 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 0.00099 ( 0 hom., cov: 32)
Exomes š: 0.000078 ( 0 hom. )
Consequence
RELN
NM_005045.4 synonymous
NM_005045.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.20
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 7-103553749-T-C is Benign according to our data. Variant chr7-103553749-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 448164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.2 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000991 (151/152324) while in subpopulation AFR AF= 0.00349 (145/41562). AF 95% confidence interval is 0.00303. There are 0 homozygotes in gnomad4. There are 73 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.5880A>G | p.Thr1960= | synonymous_variant | 39/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.5880A>G | p.Thr1960= | synonymous_variant | 39/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.5880A>G | p.Thr1960= | synonymous_variant | 39/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000992 AC: 151AN: 152206Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
151
AN:
152206
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000295 AC: 74AN: 251266Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135806
GnomAD3 exomes
AF:
AC:
74
AN:
251266
Hom.:
AF XY:
AC XY:
27
AN XY:
135806
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461690Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 49AN XY: 727178
GnomAD4 exome
AF:
AC:
114
AN:
1461690
Hom.:
Cov.:
32
AF XY:
AC XY:
49
AN XY:
727178
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000991 AC: 151AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.000980 AC XY: 73AN XY: 74486
GnomAD4 genome
?
AF:
AC:
151
AN:
152324
Hom.:
Cov.:
32
AF XY:
AC XY:
73
AN XY:
74486
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 30, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | RELN: BP4, BP7 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 02, 2017 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
RELN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 05, 2020 | 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
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at