11-47437918-G-A

Position:

chr11-47437918-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005055.5(RAPSN):c.*57C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,543,986 control chromosomes in the GnomAD database, including 13,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 975 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12461 hom. )

Consequence

RAPSN
NM_005055.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.44

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:

LOC124902673 (HGNC:):

LOC124902673 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-47437918-G-A is Benign according to our data. Variant chr11-47437918-G-A is described in ClinVar as [Benign]. Clinvar id is 304968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47437918-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAPSN	NM_005055.5 linkuse as main transcript	c.*57C>T		3_prime_UTR_variant	8/8	ENST00000298854.7
LOC124902673	XR_007062669.1 linkuse as main transcript	n.144+151G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAPSN	ENST00000298854.7 linkuse as main transcript	c.*57C>T	3_prime_UTR_variant	8/8	1	NM_005055.5	P1	Q13702-1
RAPSN	ENST00000352508.7 linkuse as main transcript	c.*57C>T	3_prime_UTR_variant	6/6	1			Q13702-2
RAPSN	ENST00000524487.5 linkuse as main transcript	c.*57C>T	3_prime_UTR_variant	7/7	5
RAPSN	ENST00000528356.1 linkuse as main transcript	n.251C>T	non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16003

AN:

152130

Hom.:

975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0639

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0880

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0380

Gnomad SAS

AF:

0.0538

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.102

AC:

15951

AN:

156074

Hom.:

1012

AF XY:

0.102

AC XY:

8365

AN XY:

82170

show subpopulations

Gnomad AFR exome

AF:

0.0654

Gnomad AMR exome

AF:

0.0596

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.0380

Gnomad SAS exome

AF:

0.0623

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.130

AC:

180280

AN:

1391738

Hom.:

12461

Cov.:

AF XY:

0.128

AC XY:

87880

AN XY:

686876

show subpopulations

Gnomad4 AFR exome

AF:

0.0617

Gnomad4 AMR exome

AF:

0.0631

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.0266

Gnomad4 SAS exome

AF:

0.0641

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.105

AC:

16005

AN:

152248

Hom.:

975

Cov.:

AF XY:

0.103

AC XY:

7650

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0637

Gnomad4 AMR

AF:

0.0878

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.0380

Gnomad4 SAS

AF:

0.0540

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.120

Hom.:

214

Bravo

AF:

0.102

Asia WGS

AF:

0.0600

AC:

207

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -

Congenital myasthenic syndrome 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Fetal akinesia deformation sequence 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Fetal akinesia deformation sequence 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.18

DANN

Benign

0.45

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