rs367881797

Variant names:

Variant summary

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

The NM_001164508.2(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_001164508.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.494

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 257759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151581472-T-C is described in Lovd as [Benign]. Variant chr2-151581472-T-C is described in Lovd as [Likely_benign].

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

GnomAD3 exomes

AF:

0.0280

AC:

3050

AN:

109098

Hom.:

AF XY:

0.0281

AC XY:

1628

AN XY:

57890

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 SAS exome

AF:

0.0306

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

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.0215

Gnomad4 ASJ exome

AF:

0.0331

Gnomad4 EAS exome

AF:

0.00248

Gnomad4 SAS exome

AF:

0.0312

Gnomad4 FIN exome

AF:

0.0263

Gnomad4 NFE exome

AF:

0.0345

Gnomad4 OTH exome

AF:

0.0334

GnomAD4 genome

AF:

0.0335

AC:

3183

AN:

94920

Hom.:

Cov.:

AF XY:

0.0331

AC XY:

1453

AN XY:

43856

show subpopulations

Gnomad4 AFR

AF:

0.0485

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.0318

Gnomad4 EAS

AF:

0.00329

Gnomad4 SAS

AF:

0.0328

Gnomad4 FIN

AF:

0.0223

Gnomad4 NFE

AF:

0.0316

Gnomad4 OTH

AF:

0.0334

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

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

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

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

DANN

Benign

0.33

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