rs546154419
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS1
The NM_005045.4(RELN):c.2779A>G(p.Met927Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,504 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 Benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
RELN
NM_005045.4 missense
NM_005045.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 7.63
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 -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, RELN
BP4
?
Computational evidence support a benign effect (MetaRNN=0.09334037).
BP6
?
Variant 7-103611727-T-C is Benign according to our data. Variant chr7-103611727-T-C is described in ClinVar as [Benign]. Clinvar id is 575123.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000046 (7/152292) while in subpopulation EAS AF= 0.00135 (7/5176). AF 95% confidence interval is 0.000634. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.2779A>G | p.Met927Val | missense_variant | 21/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.2779A>G | p.Met927Val | missense_variant | 21/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.2779A>G | p.Met927Val | missense_variant | 21/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251146Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135738
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461212Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726920
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2022 | - - |
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
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
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;P;.
Vest4
MutPred
Gain of catalytic residue at M927 (P = 0.0444);Gain of catalytic residue at M927 (P = 0.0444);Gain of catalytic residue at M927 (P = 0.0444);
MVP
MPC
ClinPred
T
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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