rs149152189
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS1
The NM_005045.4(RELN):āc.6278A>Cā(p.His2093Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,613,496 control chromosomes in the GnomAD database, including 1 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H2093Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_005045.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.6278A>C | p.His2093Pro | missense_variant | 41/65 | ENST00000428762.6 | |
RELN | NM_173054.3 | c.6278A>C | p.His2093Pro | missense_variant | 41/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.6278A>C | p.His2093Pro | missense_variant | 41/65 | 5 | NM_005045.4 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152098Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 250266Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135432
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461398Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 726960
GnomAD4 genome ? AF: 0.000204 AC: 31AN: 152098Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 19, 2016 | - - |
Seizure Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | New York Genome Center | Jan 24, 2020 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at