rs16830090

Variant names:

Variant summary

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

-20

BP4_StrongBP6_Very_StrongBA1

The NM_001164507.2(NEB):c.25405-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,604,622 control chromosomes in the GnomAD database, including 67,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5585 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61695 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.158

Publications

9 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=-0.75).

BP6

Variant 2-151485967-A-G is Benign according to our data. Variant chr2-151485967-A-G is described in ClinVar as [Benign]. Clinvar id is 257806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2 link	c.25405-34T>C		intron_variant	Intron 181 of 181	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 link	c.25405-34T>C		intron_variant	Intron 181 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.25405-34T>C		intron_variant	Intron 181 of 181	5	NM_001164508.2	ENSP00000380505.3		P20929-2
NEB	ENST00000427231.7 link	c.25405-34T>C		intron_variant	Intron 181 of 181	5	NM_001164507.2	ENSP00000416578.2		P20929-3

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38951

AN:

151970

Hom.:

5589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.295

AC:

71995

AN:

243702

AF XY:

0.292

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.287

AC:

417081

AN:

1452534

Hom.:

61695

Cov.:

AF XY:

0.286

AC XY:

206817

AN XY:

722878

show subpopulations

African (AFR)

AF:

0.130

AC:

4345

AN:

33346

American (AMR)

AF:

0.397

AC:

17682

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7780

AN:

26056

East Asian (EAS)

AF:

0.352

AC:

13938

AN:

39578

South Asian (SAS)

AF:

0.239

AC:

20579

AN:

86016

European-Finnish (FIN)

AF:

0.327

AC:

16728

AN:

51220

Middle Eastern (MID)

AF:

0.308

AC:

1774

AN:

5756

European-Non Finnish (NFE)

AF:

0.286

AC:

316772

AN:

1105932

Other (OTH)

AF:

0.291

AC:

17483

AN:

60092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

14844

29688

44531

59375

74219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10470

20940

31410

41880

52350

<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:

0.256

AC:

38975

AN:

152088

Hom.:

5585

Cov.:

AF XY:

0.262

AC XY:

19465

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.135

AC:

5597

AN:

41520

American (AMR)

AF:

0.375

AC:

5725

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1046

AN:

3470

East Asian (EAS)

AF:

0.332

AC:

1714

AN:

5166

South Asian (SAS)

AF:

0.234

AC:

1127

AN:

4824

European-Finnish (FIN)

AF:

0.323

AC:

3409

AN:

10556

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.285

AC:

19361

AN:

67978

Other (OTH)

AF:

0.265

AC:

558

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1463

2926

4388

5851

7314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.280

Hom.:

3572

Bravo

AF:

0.257

Asia WGS

AF:

0.244

AC:

849

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Nemaline myopathy 2

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arthrogryposis multiplex congenita 6

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.4

(source)

DANN

Benign

0.70

PhyloP100

0.16

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