rs111865733

chr11-47448727-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005055.5(RAPSN):c.192+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,598,058 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (30 hom.)
• Consequence: RAPSN NM_005055.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.142

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-47448727-C-T is Benign according to our data. Variant chr11-47448727-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1596/152316) while in subpopulation AFR AF= 0.0357 (1483/41582). AF 95% confidence interval is 0.0342. There are 28 homozygotes in gnomad4. There are 742 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAPSN	NM_005055.5	c.192+46G>A		intron_variant		ENST00000298854.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAPSN	ENST00000298854.7	c.192+46G>A		intron_variant		1	NM_005055.5	P1
RAPSN	ENST00000352508.7	c.192+46G>A		intron_variant		1
RAPSN	ENST00000529341.1	c.192+46G>A		intron_variant		1
RAPSN	ENST00000524487.5	c.192+46G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1590 AN: 152198 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00957

GnomAD3 exomes AF: 0.00313 AC: 734 AN: 234768 Hom.: 7 AF XY: 0.00227 AC XY: 291 AN XY: 128154

Gnomad AFR exome AF: 0.0373

Gnomad AMR exome AF: 0.00256

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000553

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.0000761

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.00122 AC: 1764 AN: 1445742 Hom.: 30 Cov.: 31 AF XY: 0.000989 AC XY: 712 AN XY: 719710

Gnomad4 AFR exome AF: 0.0360

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.0000491

Gnomad4 NFE exome AF: 0.000217

Gnomad4 OTH exome AF: 0.00287

GnomAD4 genome AF: 0.0105 AC: 1596 AN: 152316 Hom.: 28 Cov.: 32 AF XY: 0.00996 AC XY: 742 AN XY: 74478

Gnomad4 AFR AF: 0.0357

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00615 Hom.: 4

Bravo AF: 0.0122

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.1
Dann	Benign	0.75

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: rs111865733; hg19: chr11-47470279;