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11-47437768-G-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_005055.5(RAPSN):c.*207C>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 0.00841 in 692,626 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 47 hom., cov: 32)
Exomes 𝑓: 0.0059 ( 40 hom. )

Consequence

RAPSN
NM_005055.5 3_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.802
Variant links:
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 -18 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-47437768-G-T is Benign according to our data. Variant chr11-47437768-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 304966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0174 (2651/152284) while in subpopulation AFR AF= 0.0486 (2021/41542). AF 95% confidence interval is 0.0469. There are 47 homozygotes in gnomad4. There are 1296 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 46 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAPSNNM_005055.5 linkuse as main transcriptc.*207C>A 3_prime_UTR_variant 8/8 ENST00000298854.7
LOC124902673XR_007062669.1 linkuse as main transcriptn.144+1G>T splice_donor_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAPSNENST00000298854.7 linkuse as main transcriptc.*207C>A 3_prime_UTR_variant 8/81 NM_005055.5 P1Q13702-1
RAPSNENST00000352508.7 linkuse as main transcriptc.*207C>A 3_prime_UTR_variant 6/61 Q13702-2
RAPSNENST00000524487.5 linkuse as main transcriptc.*207C>A 3_prime_UTR_variant 7/75
RAPSNENST00000528356.1 linkuse as main transcriptn.401C>A non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0174
AC:
2647
AN:
152166
Hom.:
46
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0487
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00510
Gnomad ASJ
AF:
0.00374
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.0151
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00517
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00621
AC:
692
AN:
111486
Hom.:
13
AF XY:
0.00521
AC XY:
313
AN XY:
60134
show subpopulations
Gnomad AFR exome
AF:
0.0486
Gnomad AMR exome
AF:
0.00402
Gnomad ASJ exome
AF:
0.00310
Gnomad EAS exome
AF:
0.000103
Gnomad SAS exome
AF:
0.000643
Gnomad FIN exome
AF:
0.0140
Gnomad NFE exome
AF:
0.00449
Gnomad OTH exome
AF:
0.00475
GnomAD4 exome
AF:
0.00587
AC:
3173
AN:
540342
Hom.:
40
Cov.:
6
AF XY:
0.00542
AC XY:
1565
AN XY:
288502
show subpopulations
Gnomad4 AFR exome
AF:
0.0442
Gnomad4 AMR exome
AF:
0.00424
Gnomad4 ASJ exome
AF:
0.00348
Gnomad4 EAS exome
AF:
0.0000324
Gnomad4 SAS exome
AF:
0.000647
Gnomad4 FIN exome
AF:
0.0120
Gnomad4 NFE exome
AF:
0.00515
Gnomad4 OTH exome
AF:
0.00729
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0174
AC:
2651
AN:
152284
Hom.:
47
Cov.:
32
AF XY:
0.0174
AC XY:
1296
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0486
Gnomad4 AMR
AF:
0.00510
Gnomad4 ASJ
AF:
0.00374
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.0151
Gnomad4 NFE
AF:
0.00518
Gnomad4 OTH
AF:
0.00993
Alfa
AF:
0.0138
Hom.:
6
Bravo
AF:
0.0175
Asia WGS
AF:
0.00144
AC:
6
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Fetal akinesia deformation sequence 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2018- -
Congenital myasthenic syndrome 11 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
14
Dann
Benign
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73459751; hg19: chr11-47459319; API