11-47440142-G-A

Variant names:

• chr11-47440142-G-A
• rs7103835
• NM_005055.5:c.966+1017C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005055.5(RAPSN):​c.966+1017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,070 control chromosomes in the GnomAD database, including 4,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4717 hom., cov: 32)
• Consequence: RAPSN NM_005055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 12 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

LOC124902673 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 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.966+1017C>T		intron	N/A	NP_005046.2
	RAPSN	NM_001440490.1		c.966+1017C>T		intron	N/A	NP_001427419.1
	RAPSN	NM_001440491.1		c.1051+1017C>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.966+1017C>T		intron	N/A	ENSP00000298854.2	Q13702-1
	RAPSN	ENST00000352508.7	TSL:1	c.790-1211C>T		intron	N/A	ENSP00000298853.3	Q13702-2
	RAPSN	ENST00000529341.1	TSL:1	c.790-1211C>T		intron	N/A	ENSP00000431732.1	E9PK11

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33717 AN: 151950 Hom.: 4719 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33701 AN: 152070 Hom.: 4717 Cov.: 32 AF XY: 0.217 AC XY: 16161 AN XY: 74304

African (AFR) AF: 0.0547 AC: 2273 AN: 41526

American (AMR) AF: 0.200 AC: 3053 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1185 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1488 AN: 5170

South Asian (SAS) AF: 0.266 AC: 1279 AN: 4812

European-Finnish (FIN) AF: 0.232 AC: 2447 AN: 10556

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21099 AN: 67968

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.262 Hom.: 868

Bravo AF: 0.211

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
DANN	Benign	0.77
PhyloP100		-0.23
Mutation Taster		=100/0	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: rs7103835; hg19: chr11-47461693;