rs61254943

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.16705-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,566,422 control chromosomes in the GnomAD database, including 55,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5681 hom., cov: 27)

Exomes 𝑓: 0.26 ( 49998 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.367

Publications

8 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=-0.89).

BP6

Variant 2-151576372-G-A is Benign according to our data. Variant chr2-151576372-G-A is described in ClinVar as Benign. ClinVar VariationId is 95105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164507.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NEB	NM_001164507.2	MANE Plus Clinical	c.16705-18C>T	intron	N/A	NP_001157979.2
NEB	NM_001164508.2	MANE Select	c.16705-18C>T	intron	N/A	NP_001157980.2
NEB	NM_001271208.2		c.16705-18C>T	intron	N/A	NP_001258137.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NEB	ENST00000397345.8	TSL:5 MANE Select	c.16705-18C>T	intron	N/A	ENSP00000380505.3
NEB	ENST00000427231.7	TSL:5 MANE Plus Clinical	c.16705-18C>T	intron	N/A	ENSP00000416578.2
NEB	ENST00000409198.5	TSL:5	c.11602-18C>T	intron	N/A	ENSP00000386259.1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40465

AN:

149954

Hom.:

5680

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.274

GnomAD2 exomes

AF:

0.273

AC:

66584

AN:

243458

AF XY:

0.266

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.283

Gnomad NFE exome

AF:

0.260

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.261

AC:

370262

AN:

1416366

Hom.:

49998

Cov.:

AF XY:

0.259

AC XY:

181952

AN XY:

702198

show subpopulations

African (AFR)

AF:

0.252

AC:

8268

AN:

32818

American (AMR)

AF:

0.388

AC:

16672

AN:

42928

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

5865

AN:

24860

East Asian (EAS)

AF:

0.347

AC:

13624

AN:

39210

South Asian (SAS)

AF:

0.187

AC:

14724

AN:

78896

European-Finnish (FIN)

AF:

0.287

AC:

14780

AN:

51492

Middle Eastern (MID)

AF:

0.281

AC:

1390

AN:

4944

European-Non Finnish (NFE)

AF:

0.258

AC:

279316

AN:

1082964

Other (OTH)

AF:

0.268

AC:

15623

AN:

58254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

13247

26494

39742

52989

66236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9636

19272

28908

38544

48180

<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:

0.270

AC:

40478

AN:

150056

Hom.:

5681

Cov.:

AF XY:

0.272

AC XY:

19934

AN XY:

73188

show subpopulations

African (AFR)

AF:

0.249

AC:

10169

AN:

40794

American (AMR)

AF:

0.380

AC:

5714

AN:

15020

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

842

AN:

3462

East Asian (EAS)

AF:

0.321

AC:

1658

AN:

5160

South Asian (SAS)

AF:

0.188

AC:

894

AN:

4756

European-Finnish (FIN)

AF:

0.276

AC:

2751

AN:

9970

Middle Eastern (MID)

AF:

0.276

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.259

AC:

17495

AN:

67632

Other (OTH)

AF:

0.272

AC:

561

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

1421

2841

4262

5682

7103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.229

Hom.:

1396

Bravo

AF:

0.280

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Nemaline myopathy 2 (2)

not provided (2)

Arthrogryposis multiplex congenita 6 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.1

(source)

DANN

Benign

0.24

PhyloP100

0.37

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over