11-47438755-A-G

Position:

chr11-47438755-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005055.5(RAPSN):c.1143T>C(p.Pro381=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,562,730 control chromosomes in the GnomAD database, including 382,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 31106 hom., cov: 32)

Exomes 𝑓: 0.70 ( 351469 hom. )

Consequence

RAPSN
NM_005055.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.206

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 links:

LOC124902673 (HGNC:):

LOC124902673 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 11-47438755-A-G is Benign according to our data. Variant chr11-47438755-A-G is described in ClinVar as [Benign]. Clinvar id is 130089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47438755-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.206 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPSN	NM_005055.5 linkuse as main transcript	c.1143T>C	p.Pro381=	synonymous_variant	7/8	ENST00000298854.7	NP_005046.2
LOC124902673	XR_007062669.1 linkuse as main transcript	n.144+988A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPSN	ENST00000298854.7 linkuse as main transcript	c.1143T>C	p.Pro381=	synonymous_variant	7/8	1	NM_005055.5	ENSP00000298854	P1	Q13702-1

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

94917

AN:

151888

Hom.:

31092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.659

Gnomad SAS

AF:

0.784

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.684

GnomAD3 exomes

AF:

0.664

AC:

121435

AN:

182762

Hom.:

41338

AF XY:

0.678

AC XY:

65901

AN XY:

97248

show subpopulations

Gnomad AFR exome

AF:

0.396

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.719

Gnomad EAS exome

AF:

0.623

Gnomad SAS exome

AF:

0.773

Gnomad FIN exome

AF:

0.611

Gnomad NFE exome

AF:

0.704

Gnomad OTH exome

AF:

0.720

GnomAD4 exome

AF:

0.703

AC:

991432

AN:

1410724

Hom.:

351469

Cov.:

AF XY:

0.706

AC XY:

491249

AN XY:

695834

show subpopulations

Gnomad4 AFR exome

AF:

0.407

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.720

Gnomad4 EAS exome

AF:

0.593

Gnomad4 SAS exome

AF:

0.768

Gnomad4 FIN exome

AF:

0.623

Gnomad4 NFE exome

AF:

0.717

Gnomad4 OTH exome

AF:

0.707

GnomAD4 genome

AF:

0.625

AC:

94972

AN:

152006

Hom.:

31106

Cov.:

AF XY:

0.623

AC XY:

46278

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.669

Gnomad4 ASJ

AF:

0.716

Gnomad4 EAS

AF:

0.658

Gnomad4 SAS

AF:

0.783

Gnomad4 FIN

AF:

0.607

Gnomad4 NFE

AF:

0.720

Gnomad4 OTH

AF:

0.688

Alfa

AF:

0.711

Hom.:

59455

Bravo

AF:

0.617

Asia WGS

AF:

0.720

AC:

2508

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 2016	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. -

Congenital myasthenic syndrome 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Fetal akinesia deformation sequence 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital myasthenic syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Fetal akinesia deformation sequence 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.6

DANN

Benign

0.77

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over