rs7103835

Positions:

• chr11-47440142-G-A
• chr11-47440142-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000298854.7(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 ENST00000298854.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPSN	NM_005055.5	c.966+1017C>T		intron_variant		ENST00000298854.7	NP_005046.2
LOC124902673	XR_007062669.1	n.144+2375G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPSN	ENST00000298854.7	c.966+1017C>T		intron_variant		1	NM_005055.5	ENSP00000298854	P1

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

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.263

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
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

Other links and lift over

dbSNP: rs7103835; hg19: chr11-47461693;