rs34729771

Positions:

• chr11-47441931-AG-A
• chr11-47441931-AG-AGG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000298854.7(RAPSN):​c.691-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (30441 hom., cov: 0)
  • Exomes 𝑓: 0.70 (351164 hom.)
• Consequence: RAPSN ENST00000298854.7 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.0750

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]

LOC124902673 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-47441931-AG-A is Benign according to our data. Variant chr11-47441931-AG-A is described in ClinVar as [Benign]. Clinvar id is 197249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47441931-AG-A is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
RAPSN	NM_005055.5	c.691-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000298854.7	NP_005046.2
LOC124902673	XR_007062669.1	n.144+4166del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPSN	ENST00000298854.7	c.691-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005055.5	ENSP00000298854	P1
RAPSN	ENST00000352508.7	c.691-11del		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000298853
RAPSN	ENST00000529341.1	c.691-11del		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000431732
RAPSN	ENST00000524487.5	c.532-11del		splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000435551

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93335 AN: 152042 Hom.: 30426 Cov.: 0

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.673

GnomAD3 exomes AF: 0.679 AC: 114250 AN: 168348 Hom.: 39600 AF XY: 0.693 AC XY: 63450 AN XY: 91540

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.618

Gnomad ASJ exome AF: 0.723

Gnomad EAS exome AF: 0.642

Gnomad SAS exome AF: 0.778

Gnomad FIN exome AF: 0.605

Gnomad NFE exome AF: 0.722

Gnomad OTH exome AF: 0.724

GnomAD4 exome AF: 0.703 AC: 989419 AN: 1407860 Hom.: 351164 Cov.: 0 AF XY: 0.706 AC XY: 491770 AN XY: 696436

Gnomad4 AFR exome AF: 0.372

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.720

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.717

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.614 AC: 93390 AN: 152160 Hom.: 30441 Cov.: 0 AF XY: 0.613 AC XY: 45596 AN XY: 74396

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.677

Alfa AF: 0.686 Hom.: 6621

Bravo AF: 0.604

Asia WGS AF: 0.720 AC: 2505 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 21, 2015	- -

Congenital Myasthenic Syndrome, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Fetal akinesia deformation sequence 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 31, 2018

- -

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

- -

Fetal akinesia deformation sequence 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Congenital myasthenic syndrome Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Congenital myasthenic syndrome 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs34729771; hg19: chr11-47463483;