rs367881797

Variant names:

Variant summary

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

The NM_001164507.2(NEB):c.16284+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 65 hom., cov: 11)

Exomes 𝑓: 0.032 ( 434 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.494

Publications

0 publications found

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]

NEB Gene-Disease associations (from GenCC):

nemaline myopathy 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Ambry Genetics
childhood-onset nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
intermediate nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
typical nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
lethal multiple pterygium syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
severe congenital nemaline myopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NEB links:

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=-0.94).

BP6

Variant 2-151581472-T-C is Benign according to our data. Variant chr2-151581472-T-C is described in ClinVar as Benign. ClinVar VariationId is 257759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2 link	c.16284+11A>G		intron_variant	Intron 103 of 181	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 link	c.16284+11A>G		intron_variant	Intron 103 of 181	ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NEB	ENST00000397345.8 link	c.16284+11A>G	intron_variant	Intron 103 of 181	5	NM_001164508.2	ENSP00000380505.3	P20929-2
NEB	ENST00000427231.7 link	c.16284+11A>G	intron_variant	Intron 103 of 181	5	NM_001164507.2	ENSP00000416578.2	P20929-3
NEB	ENST00000409198.5 link	c.11602-5118A>G	intron_variant	Intron 78 of 149	5		ENSP00000386259.1	P20929-4
NEB	ENST00000413693.5 link	c.474+11A>G	intron_variant	Intron 3 of 73	5		ENSP00000410961.1	H0Y786

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

3175

AN:

94810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.0331

Gnomad AMR

AF:

0.0214

Gnomad ASJ

AF:

0.0318

Gnomad EAS

AF:

0.00329

Gnomad SAS

AF:

0.0310

Gnomad FIN

AF:

0.0223

Gnomad MID

AF:

0.0546

Gnomad NFE

AF:

0.0316

Gnomad OTH

AF:

0.0340

GnomAD2 exomes

AF:

0.0280

AC:

3050

AN:

109098

AF XY:

0.0281

show subpopulations

Gnomad AFR exome

AF:

0.0522

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.0232

Gnomad NFE exome

AF:

0.0332

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0321

AC:

20742

AN:

646124

Hom.:

434

Cov.:

AF XY:

0.0322

AC XY:

10840

AN XY:

336482

show subpopulations

African (AFR)

AF:

0.0559

AC:

914

AN:

16340

American (AMR)

AF:

0.0215

AC:

625

AN:

29082

Ashkenazi Jewish (ASJ)

AF:

0.0331

AC:

604

AN:

18254

East Asian (EAS)

AF:

0.00248

AC:

AN:

29854

South Asian (SAS)

AF:

0.0312

AC:

1686

AN:

54076

European-Finnish (FIN)

AF:

0.0263

AC:

1205

AN:

45750

Middle Eastern (MID)

AF:

0.0552

AC:

133

AN:

2408

European-Non Finnish (NFE)

AF:

0.0345

AC:

14436

AN:

418484

Other (OTH)

AF:

0.0334

AC:

1065

AN:

31876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

955

1910

2864

3819

4774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.0335

AC:

3183

AN:

94920

Hom.:

Cov.:

AF XY:

0.0331

AC XY:

1453

AN XY:

43856

show subpopulations

African (AFR)

AF:

0.0485

AC:

1116

AN:

23012

American (AMR)

AF:

0.0212

AC:

171

AN:

8058

Ashkenazi Jewish (ASJ)

AF:

0.0318

AC:

AN:

2614

East Asian (EAS)

AF:

0.00329

AC:

AN:

3042

South Asian (SAS)

AF:

0.0328

AC:

AN:

2104

European-Finnish (FIN)

AF:

0.0223

AC:

113

AN:

5060

Middle Eastern (MID)

AF:

0.0541

AC:

AN:

222

European-Non Finnish (NFE)

AF:

0.0316

AC:

1550

AN:

49036

Other (OTH)

AF:

0.0334

AC:

AN:

1078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

145

289

434

578

723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0384

Hom.:

Bravo

AF:

0.0387

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 26, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.037

(source)

DANN

Benign

0.33

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over