Variant 11-47448727-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.142

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPSN	NM_005055.5 link	c.192+46G>A		intron_variant		ENST00000298854.7	NP_005046.2	Q13702-1A0A0S2Z4F8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RAPSN	ENST00000298854.7 link	c.192+46G>A	intron_variant	1	NM_005055.5	ENSP00000298854.2	Q13702-1
RAPSN	ENST00000352508.7 link	c.192+46G>A	intron_variant	1		ENSP00000298853.3	Q13702-2
RAPSN	ENST00000529341.1 link	c.192+46G>A	intron_variant	1		ENSP00000431732.1	E9PK11
RAPSN	ENST00000524487.5 link	c.192+46G>A	intron_variant	5		ENSP00000435551.2	E9PJP9

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1590

AN:

152198

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00227

AC XY:

291

AN XY:

128154

show subpopulations

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.:

Cov.:

AF XY:

0.000989

AC XY:

712

AN XY:

719710

show subpopulations

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.:

Cov.:

AF XY:

0.00996

AC XY:

742

AN XY:

74478

show subpopulations

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.:

Bravo

AF:

0.0122

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over