rs16830128

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.23241+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,424,300 control chromosomes in the GnomAD database, including 766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 79 hom., cov: 32)

Exomes 𝑓: 0.011 ( 687 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0610

Publications

4 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 links:

RIF1 (HGNC:23207): (replication timing regulatory factor 1) This gene encodes a protein that shares homology with the yeast teleomere binding protein, Rap1 interacting factor 1. This protein localizes to aberrant telomeres may be involved in DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

RIF1 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=-0.86).

BP6

Variant 2-151513538-A-G is Benign according to our data. Variant chr2-151513538-A-G is described in ClinVar as Benign. ClinVar VariationId is 257798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2 link	c.23241+42T>C		intron_variant	Intron 160 of 181	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 link	c.23241+42T>C		intron_variant	Intron 160 of 181	ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEB	ENST00000397345.8 link	c.23241+42T>C		intron_variant	Intron 160 of 181	5	NM_001164508.2	ENSP00000380505.3
NEB	ENST00000427231.7 link	c.23241+42T>C		intron_variant	Intron 160 of 181	5	NM_001164507.2	ENSP00000416578.2

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2227

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0755

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00195

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.0233

AC:

4180

AN:

179392

AF XY:

0.0259

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.0315

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.0000559

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0111

AC:

14144

AN:

1272012

Hom.:

687

Cov.:

AF XY:

0.0129

AC XY:

8209

AN XY:

635660

show subpopulations

African (AFR)

AF:

0.0169

AC:

498

AN:

29450

American (AMR)

AF:

0.00289

AC:

105

AN:

36378

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

755

AN:

24246

East Asian (EAS)

AF:

0.136

AC:

5061

AN:

37140

South Asian (SAS)

AF:

0.0679

AC:

5208

AN:

76680

European-Finnish (FIN)

AF:

0.000277

AC:

AN:

50538

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

5400

European-Non Finnish (NFE)

AF:

0.00147

AC:

1405

AN:

958326

Other (OTH)

AF:

0.0191

AC:

1029

AN:

53854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

645

1290

1935

2580

3225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

0.0148

AC:

2261

AN:

152288

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1204

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0175

AC:

729

AN:

41560

American (AMR)

AF:

0.00752

AC:

115

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

108

AN:

3468

East Asian (EAS)

AF:

0.142

AC:

732

AN:

5168

South Asian (SAS)

AF:

0.0764

AC:

369

AN:

4828

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00196

AC:

133

AN:

68028

Other (OTH)

AF:

0.0336

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

109

219

328

438

547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00774

Hom.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.124

AC:

428

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

2.8

(source)

DANN

Benign

0.63

PhyloP100

-0.061

PromoterAI

-0.0042

Neutral

(source)

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