rs7111873

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005055.5(RAPSN):c.456T>C(p.Tyr152Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,612,224 control chromosomes in the GnomAD database, including 397,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31209 hom., cov: 31)

Exomes 𝑓: 0.71 ( 366575 hom. )

Consequence

RAPSN
NM_005055.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.05

Publications

28 publications found

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]

RAPSN Gene-Disease associations (from GenCC):

fetal akinesia deformation sequence 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
neuromuscular disease
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
congenital myasthenic syndrome 11
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp
fetal akinesia deformation sequence 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RAPSN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-47447887-A-G is Benign according to our data. Variant chr11-47447887-A-G is described in ClinVar as Benign. ClinVar VariationId is 130091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPSN	NM_005055.5 link	c.456T>C	p.Tyr152Tyr	synonymous_variant	Exon 2 of 8	ENST00000298854.7	NP_005046.2	Q13702-1A0A0S2Z4F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAPSN	ENST00000298854.7 link	c.456T>C	p.Tyr152Tyr	synonymous_variant	Exon 2 of 8	1	NM_005055.5	ENSP00000298854.2	Q13702-1
RAPSN	ENST00000352508.7 link	c.456T>C	p.Tyr152Tyr	synonymous_variant	Exon 2 of 6	1		ENSP00000298853.3	Q13702-2
RAPSN	ENST00000529341.1 link	c.456T>C	p.Tyr152Tyr	synonymous_variant	Exon 2 of 5	1		ENSP00000431732.1	E9PK11
RAPSN	ENST00000524487.5 link	c.456T>C	p.Tyr152Tyr	synonymous_variant	Exon 2 of 7	5		ENSP00000435551.2	E9PJP9

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95043

AN:

151872

Hom.:

31192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.661

Gnomad SAS

AF:

0.785

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.721

Gnomad OTH

AF:

0.685

GnomAD2 exomes

AF:

0.680

AC:

168439

AN:

247528

AF XY:

0.694

show subpopulations

Gnomad AFR exome

AF:

0.414

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.720

Gnomad EAS exome

AF:

0.646

Gnomad FIN exome

AF:

0.619

Gnomad NFE exome

AF:

0.723

Gnomad OTH exome

AF:

0.722

GnomAD4 exome

AF:

0.706

AC:

1030270

AN:

1460234

Hom.:

366575

Cov.:

AF XY:

0.709

AC XY:

515005

AN XY:

726378

show subpopulations

African (AFR)

AF:

0.409

AC:

13692

AN:

33446

American (AMR)

AF:

0.625

AC:

27794

AN:

44456

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

18796

AN:

26116

East Asian (EAS)

AF:

0.601

AC:

23831

AN:

39656

South Asian (SAS)

AF:

0.770

AC:

66331

AN:

86140

European-Finnish (FIN)

AF:

0.625

AC:

33058

AN:

52866

Middle Eastern (MID)

AF:

0.744

AC:

4288

AN:

5766

European-Non Finnish (NFE)

AF:

0.719

AC:

799602

AN:

1111462

Other (OTH)

AF:

0.711

AC:

42878

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

19909

39818

59727

79636

99545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19798

39596

59394

79192

98990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.626

AC:

95101

AN:

151990

Hom.:

31209

Cov.:

AF XY:

0.624

AC XY:

46332

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.418

AC:

17327

AN:

41426

American (AMR)

AF:

0.670

AC:

10214

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.716

AC:

2486

AN:

3470

East Asian (EAS)

AF:

0.660

AC:

3408

AN:

5164

South Asian (SAS)

AF:

0.783

AC:

3779

AN:

4824

European-Finnish (FIN)

AF:

0.606

AC:

6414

AN:

10586

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.721

AC:

49017

AN:

67952

Other (OTH)

AF:

0.689

AC:

1452

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1741

3482

5222

6963

8704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.694

Hom.:

25645

Bravo

AF:

0.618

Asia WGS

AF:

0.720

AC:

2509

AN:

3478

EpiCase

AF:

0.736

EpiControl

AF:

0.737

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Dec 07, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Congenital myasthenic syndrome 11

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 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. -

Fetal akinesia deformation sequence 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Fetal akinesia deformation sequence 1;C4225367:Congenital myasthenic syndrome 11

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Fetal akinesia deformation sequence 2

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.016

(source)

DANN

Benign

0.41

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over