rs45547231

Variant names:

• chr11-47448165-G-A
• rs45547231
• NM_005055.5:c.193-15C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-47448165-G-A
• chr11-47448165-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005055.5(RAPSN):​c.193-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,605,420 control chromosomes in the GnomAD database, including 13,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1020 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12818 hom.)
• Consequence: RAPSN NM_005055.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.360
• Publications: 10 publications found

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: Labcorp Genetics (formerly Invitae), G2P
• neuromuscular disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• congenital myasthenic syndrome 11

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-47448165-G-A is Benign according to our data. Variant chr11-47448165-G-A is described in ClinVar as Benign. ClinVar VariationId is 259627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005055.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPSN	NM_005055.5	MANE Select	c.193-15C>T		intron	N/A	NP_005046.2
	RAPSN	NM_001440490.1		c.193-15C>T		intron	N/A	NP_001427419.1
	RAPSN	NM_001440491.1		c.193-15C>T		intron	N/A	NP_001427420.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPSN	ENST00000298854.7	TSL:1 MANE Select	c.193-15C>T		intron	N/A	ENSP00000298854.2	Q13702-1
	RAPSN	ENST00000352508.7	TSL:1	c.193-15C>T		intron	N/A	ENSP00000298853.3	Q13702-2
	RAPSN	ENST00000529341.1	TSL:1	c.193-15C>T		intron	N/A	ENSP00000431732.1	E9PK11

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16714 AN: 151986 Hom.: 1018 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0382

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.106 AC: 25584 AN: 241002 AF XY: 0.107

Gnomad AFR exome AF: 0.0884

Gnomad AMR exome AF: 0.0565

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0353

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.128 AC: 186686 AN: 1453316 Hom.: 12818 Cov.: 36 AF XY: 0.127 AC XY: 91842 AN XY: 723148

African (AFR) AF: 0.0830 AC: 2777 AN: 33470

American (AMR) AF: 0.0603 AC: 2693 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3767 AN: 26124

East Asian (EAS) AF: 0.0268 AC: 1064 AN: 39680

South Asian (SAS) AF: 0.0637 AC: 5491 AN: 86178

European-Finnish (FIN) AF: 0.137 AC: 6265 AN: 45776

Middle Eastern (MID) AF: 0.130 AC: 748 AN: 5768

European-Non Finnish (NFE) AF: 0.141 AC: 156564 AN: 1111390

Other (OTH) AF: 0.121 AC: 7317 AN: 60296

GnomAD4 genome AF: 0.110 AC: 16725 AN: 152104 Hom.: 1020 Cov.: 32 AF XY: 0.107 AC XY: 7976 AN XY: 74364

African (AFR) AF: 0.0840 AC: 3484 AN: 41496

American (AMR) AF: 0.0851 AC: 1300 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3470

East Asian (EAS) AF: 0.0383 AC: 198 AN: 5168

South Asian (SAS) AF: 0.0543 AC: 262 AN: 4822

European-Finnish (FIN) AF: 0.127 AC: 1347 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9340 AN: 67946

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.123 Hom.: 262

Bravo AF: 0.107

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Congenital myasthenic syndrome 11 (2)
-	-	1	Congenital myasthenic syndrome (1)
-	-	1	Fetal akinesia deformation sequence 1 (1)
-	-	1	Fetal akinesia deformation sequence 1;C4225367:Congenital myasthenic syndrome 11 (1)
-	-	1	Fetal akinesia deformation sequence 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.84
PhyloP100		-0.36
Mutation Taster		=46/38	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45547231; hg19: chr11-47469717; COSMIC: COSV54085037;