rs886038442

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4BP6_Moderate

The NM_001164507.2(NEB):​c.14633G>A​(p.Arg4878His) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00017 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NEB
NM_001164507.2 missense

Scores

1
2
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.86
Variant links:
Genes affected
NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.27297032).
BP6
Variant 2-151593104-C-T is Benign according to our data. Variant chr2-151593104-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257742.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEBNM_001164507.2 linkuse as main transcriptc.14633G>A p.Arg4878His missense_variant 94/182 ENST00000427231.7
NEBNM_001164508.2 linkuse as main transcriptc.14633G>A p.Arg4878His missense_variant 94/182 ENST00000397345.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEBENST00000397345.8 linkuse as main transcriptc.14633G>A p.Arg4878His missense_variant 94/1825 NM_001164508.2 P5P20929-2
NEBENST00000427231.7 linkuse as main transcriptc.14633G>A p.Arg4878His missense_variant 94/1825 NM_001164507.2 A2P20929-3
NEBENST00000409198.5 linkuse as main transcriptc.11601+16705G>A intron_variant 5 P20929-4

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
66
Hom.:
0
Cov.:
0
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad NFE
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000168
AC:
19
AN:
113280
Hom.:
0
Cov.:
0
AF XY:
0.000182
AC XY:
11
AN XY:
60456
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000146
Gnomad4 ASJ exome
AF:
0.000287
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000258
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
66
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
40
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Uncertain
23
DANN
Benign
0.89
DEOGEN2
Benign
0.021
.;T;.;.;.
Eigen
Benign
0.084
Eigen_PC
Benign
-0.025
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.73
T;T;T;.;.
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.27
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.98
D;D;D;D
PROVEAN
Benign
-0.12
N;.;N;.;.
REVEL
Benign
0.15
Sift
Uncertain
0.0050
D;.;D;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D
Vest4
0.41
MutPred
0.51
Loss of MoRF binding (P = 0.0123);Loss of MoRF binding (P = 0.0123);Loss of MoRF binding (P = 0.0123);Loss of MoRF binding (P = 0.0123);Loss of MoRF binding (P = 0.0123);
MVP
0.51
MPC
0.37
ClinPred
0.32
T
GERP RS
2.6
gMVP
0.014

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.

Other links and lift over

dbSNP: rs886038442; hg19: chr2-152449618; API