rs149613347
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_005045.4(RELN):āc.9340A>Gā(p.Ile3114Val) variant causes a missense change. The variant allele was found at a frequency of 0.000249 in 1,614,002 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00028 ( 2 hom., cov: 32)
Exomes š: 0.00025 ( 0 hom. )
Consequence
RELN
NM_005045.4 missense
NM_005045.4 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.74
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 -8 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, RELN
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009862274).
BP6
?
Variant 7-103495752-T-C is Benign according to our data. Variant chr7-103495752-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 95236.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=1, Uncertain_significance=1}.
BS2
?
High Homozygotes in GnomAd4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.9340A>G | p.Ile3114Val | missense_variant | 57/65 | ENST00000428762.6 | |
SLC26A5-AS1 | NR_110141.1 | n.1366-8652T>C | intron_variant, non_coding_transcript_variant | ||||
RELN | NM_173054.3 | c.9340A>G | p.Ile3114Val | missense_variant | 57/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.9340A>G | p.Ile3114Val | missense_variant | 57/65 | 5 | NM_005045.4 | P5 | |
SLC26A5-AS1 | ENST00000422488.1 | n.1366-8652T>C | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152196Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000458 AC: 115AN: 251306Hom.: 1 AF XY: 0.000456 AC XY: 62AN XY: 135822
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GnomAD4 exome AF: 0.000246 AC: 359AN: 1461806Hom.: 0 Cov.: 32 AF XY: 0.000253 AC XY: 184AN XY: 727202
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GnomAD4 genome ? AF: 0.000283 AC: 43AN: 152196Hom.: 2 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74366
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Norman-Roberts syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 01, 2017 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 22, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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