rs371201870
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_001164507.2(NEB):c.20946A>G(p.Lys6982Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
NEB
NM_001164507.2 synonymous
NM_001164507.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.854
Publications
0 publications found
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]
NEB Gene-Disease associations (from GenCC):
- nemaline myopathy 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Ambry Genetics
- childhood-onset nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- intermediate nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- typical nemaline myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- lethal multiple pterygium syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- severe congenital nemaline myopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 2-151538191-T-C is Benign according to our data. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151538191-T-C is described in CliVar as Likely_benign. Clinvar id is 534058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.854 with no splicing effect.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.20946A>G | p.Lys6982Lys | synonymous_variant | Exon 139 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
NEB | ENST00000427231.7 | c.20946A>G | p.Lys6982Lys | synonymous_variant | Exon 139 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 |
Frequencies
GnomAD3 genomes AF: 0.000296 AC: 45AN: 152210Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
45
AN:
152210
Hom.:
Cov.:
32
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GnomAD2 exomes AF: 0.0000321 AC: 8AN: 248894 AF XY: 0.0000148 show subpopulations
GnomAD2 exomes
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AC:
8
AN:
248894
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461046Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 726852 show subpopulations
GnomAD4 exome
AF:
AC:
37
AN:
1461046
Hom.:
Cov.:
30
AF XY:
AC XY:
18
AN XY:
726852
show subpopulations
African (AFR)
AF:
AC:
30
AN:
33452
American (AMR)
AF:
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26126
East Asian (EAS)
AF:
AC:
0
AN:
39680
South Asian (SAS)
AF:
AC:
0
AN:
86232
European-Finnish (FIN)
AF:
AC:
0
AN:
53362
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111360
Other (OTH)
AF:
AC:
6
AN:
60350
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.437
Heterozygous variant carriers
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Age Distribution
Exome Het
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Age
GnomAD4 genome AF: 0.000295 AC: 45AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74484 show subpopulations
GnomAD4 genome
AF:
AC:
45
AN:
152328
Hom.:
Cov.:
32
AF XY:
AC XY:
22
AN XY:
74484
show subpopulations
African (AFR)
AF:
AC:
42
AN:
41584
American (AMR)
AF:
AC:
3
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68034
Other (OTH)
AF:
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.509
Heterozygous variant carriers
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Nemaline myopathy 2 Benign:1
Jan 24, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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