chr11-47437764-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_005055.5(RAPSN):c.*211G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 667,640 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 2 hom. )
Consequence
RAPSN
NM_005055.5 3_prime_UTR
NM_005055.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.115
Genes affected
RAPSN (HGNC:9863): (receptor associated protein of the synapse) This gene encodes a member of a family of proteins that are receptor associated proteins of the synapse. The encoded protein contains a conserved cAMP-dependent protein kinase phosphorylation site, and plays a critical role in clustering and anchoring nicotinic acetylcholine receptors at synaptic sites by linking the receptors to the underlying postsynaptic cytoskeleton, possibly by direct association with actin or spectrin. Mutations in this gene may play a role in postsynaptic congenital myasthenic syndromes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00259 (394/152196) while in subpopulation NFE AF= 0.00401 (273/68040). AF 95% confidence interval is 0.00362. There are 0 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAPSN | NM_005055.5 | c.*211G>A | 3_prime_UTR_variant | 8/8 | ENST00000298854.7 | ||
LOC124902673 | XR_007062669.1 | n.141C>T | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAPSN | ENST00000298854.7 | c.*211G>A | 3_prime_UTR_variant | 8/8 | 1 | NM_005055.5 | P1 | ||
RAPSN | ENST00000352508.7 | c.*211G>A | 3_prime_UTR_variant | 6/6 | 1 | ||||
RAPSN | ENST00000528356.1 | n.405G>A | non_coding_transcript_exon_variant | 2/2 | 3 | ||||
RAPSN | ENST00000524487.5 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00259 AC: 394AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00252 AC: 257AN: 101884Hom.: 1 AF XY: 0.00236 AC XY: 129AN XY: 54630
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GnomAD4 exome AF: 0.00315 AC: 1626AN: 515444Hom.: 2 Cov.: 6 AF XY: 0.00292 AC XY: 799AN XY: 273984
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GnomAD4 genome AF: 0.00259 AC: 394AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.00249 AC XY: 185AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fetal akinesia deformation sequence 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Congenital myasthenic syndrome 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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