2-151561167-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001164508.2(NEB):​c.19101+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,573,978 control chromosomes in the GnomAD database, including 1,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 647 hom., cov: 32)
Exomes 𝑓: 0.015 ( 1225 hom. )

Consequence

NEB
NM_001164508.2 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0660
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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 2-151561167-G-A is Benign according to our data. Variant chr2-151561167-G-A is described in ClinVar as [Benign]. Clinvar id is 257777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEBNM_001164507.2 linkc.19101+41C>T intron_variant Intron 122 of 181 ENST00000427231.7 NP_001157979.2
NEBNM_001164508.2 linkc.19101+41C>T intron_variant Intron 122 of 181 ENST00000397345.8 NP_001157980.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEBENST00000397345.8 linkc.19101+41C>T intron_variant Intron 122 of 181 5 NM_001164508.2 ENSP00000380505.3 P20929-2
NEBENST00000427231.7 linkc.19101+41C>T intron_variant Intron 122 of 181 5 NM_001164507.2 ENSP00000416578.2 P20929-3

Frequencies

GnomAD3 genomes
AF:
0.0549
AC:
8355
AN:
152066
Hom.:
635
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.157
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0231
Gnomad ASJ
AF:
0.0320
Gnomad EAS
AF:
0.145
Gnomad SAS
AF:
0.0767
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.00221
Gnomad OTH
AF:
0.0517
GnomAD2 exomes
AF:
0.0336
AC:
7473
AN:
222124
AF XY:
0.0333
show subpopulations
Gnomad AFR exome
AF:
0.164
Gnomad AMR exome
AF:
0.0106
Gnomad ASJ exome
AF:
0.0325
Gnomad EAS exome
AF:
0.147
Gnomad FIN exome
AF:
0.000149
Gnomad NFE exome
AF:
0.00231
Gnomad OTH exome
AF:
0.0205
GnomAD4 exome
AF:
0.0151
AC:
21531
AN:
1421794
Hom.:
1225
Cov.:
27
AF XY:
0.0163
AC XY:
11554
AN XY:
707032
show subpopulations
African (AFR)
AF:
0.167
AC:
5453
AN:
32634
American (AMR)
AF:
0.0110
AC:
464
AN:
41998
Ashkenazi Jewish (ASJ)
AF:
0.0325
AC:
829
AN:
25540
East Asian (EAS)
AF:
0.139
AC:
5434
AN:
39122
South Asian (SAS)
AF:
0.0679
AC:
5678
AN:
83616
European-Finnish (FIN)
AF:
0.000344
AC:
18
AN:
52338
Middle Eastern (MID)
AF:
0.0196
AC:
111
AN:
5658
European-Non Finnish (NFE)
AF:
0.00167
AC:
1802
AN:
1081906
Other (OTH)
AF:
0.0295
AC:
1742
AN:
58982
Heterozygous variant carriers
0
1012
2023
3035
4046
5058
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
352
704
1056
1408
1760
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0552
AC:
8398
AN:
152184
Hom.:
647
Cov.:
32
AF XY:
0.0552
AC XY:
4108
AN XY:
74416
show subpopulations
African (AFR)
AF:
0.157
AC:
6519
AN:
41488
American (AMR)
AF:
0.0231
AC:
353
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.0320
AC:
111
AN:
3472
East Asian (EAS)
AF:
0.146
AC:
755
AN:
5176
South Asian (SAS)
AF:
0.0774
AC:
373
AN:
4822
European-Finnish (FIN)
AF:
0.0000942
AC:
1
AN:
10616
Middle Eastern (MID)
AF:
0.0238
AC:
7
AN:
294
European-Non Finnish (NFE)
AF:
0.00221
AC:
150
AN:
68004
Other (OTH)
AF:
0.0611
AC:
129
AN:
2110
Heterozygous variant carriers
0
358
716
1075
1433
1791
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
92
184
276
368
460
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0175
Hom.:
58
Bravo
AF:
0.0613
Asia WGS
AF:
0.139
AC:
482
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.28
DANN
Benign
0.54
Mutation Taster
=100/0
polymorphism (auto)

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: rs4364020; hg19: chr2-152417681; COSMIC: COSV51419733; API