NM_001164507.2:c.10872+27A>C

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.10872+27A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,558,888 control chromosomes in the GnomAD database, including 107,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7955 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99771 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.322

Publications

6 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 2-151619424-T-G is Benign according to our data. Variant chr2-151619424-T-G is described in ClinVar as Benign. ClinVar VariationId is 257720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 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.10872+27A>C	intron	N/A	NP_001157979.2
NEB	NM_001164508.2	MANE Select	c.10872+27A>C	intron	N/A	NP_001157980.2
NEB	NM_001271208.2		c.10872+27A>C	intron	N/A	NP_001258137.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NEB	ENST00000397345.8	TSL:5 MANE Select	c.10872+27A>C	intron	N/A	ENSP00000380505.3
NEB	ENST00000427231.7	TSL:5 MANE Plus Clinical	c.10872+27A>C	intron	N/A	ENSP00000416578.2
NEB	ENST00000409198.5	TSL:5	c.10143+27A>C	intron	N/A	ENSP00000386259.1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47312

AN:

151992

Hom.:

7951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.314

GnomAD2 exomes

AF:

0.337

AC:

73263

AN:

217256

AF XY:

0.336

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.267

Gnomad EAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.371

AC:

522277

AN:

1406778

Hom.:

99771

Cov.:

AF XY:

0.368

AC XY:

254321

AN XY:

691998

show subpopulations

African (AFR)

AF:

0.174

AC:

5626

AN:

32306

American (AMR)

AF:

0.345

AC:

14265

AN:

41350

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

6043

AN:

22882

East Asian (EAS)

AF:

0.259

AC:

10092

AN:

39040

South Asian (SAS)

AF:

0.229

AC:

17655

AN:

77074

European-Finnish (FIN)

AF:

0.390

AC:

20080

AN:

51428

Middle Eastern (MID)

AF:

0.329

AC:

1726

AN:

5250

European-Non Finnish (NFE)

AF:

0.395

AC:

426719

AN:

1079394

Other (OTH)

AF:

0.346

AC:

20071

AN:

58054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

17009

34017

51026

68034

85043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13410

26820

40230

53640

67050

<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:

0.311

AC:

47334

AN:

152110

Hom.:

7955

Cov.:

AF XY:

0.310

AC XY:

23047

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.175

AC:

7281

AN:

41516

American (AMR)

AF:

0.310

AC:

4732

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

867

AN:

3470

East Asian (EAS)

AF:

0.247

AC:

1279

AN:

5172

South Asian (SAS)

AF:

0.235

AC:

1132

AN:

4820

European-Finnish (FIN)

AF:

0.402

AC:

4251

AN:

10572

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.395

AC:

26863

AN:

67970

Other (OTH)

AF:

0.311

AC:

656

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1653

3305

4958

6610

8263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.238

Hom.:

1032

Bravo

AF:

0.300

Asia WGS

AF:

0.244

AC:

849

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Arthrogryposis multiplex congenita 6 (1)

Nemaline myopathy 2 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.088

(source)

DANN

Benign

0.31

PhyloP100

-0.32

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

Computational scores

Splicing

Publications

Other links and lift over