NM_001164507.2:c.24874-47A>T

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.24874-47A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,593,840 control chromosomes in the GnomAD database, including 89,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6203 hom., cov: 31)

Exomes 𝑓: 0.33 ( 83752 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.887

Publications

11 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=-0.82).

BP6

Variant 2-151492328-T-A is Benign according to our data. Variant chr2-151492328-T-A is described in ClinVar as Benign. ClinVar VariationId is 257804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2 link	c.24874-47A>T		intron_variant	Intron 177 of 181	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 link	c.24874-47A>T		intron_variant	Intron 177 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.24874-47A>T		intron_variant	Intron 177 of 181	5	NM_001164508.2	ENSP00000380505.3		P20929-2
NEB	ENST00000427231.7 link	c.24874-47A>T		intron_variant	Intron 177 of 181	5	NM_001164507.2	ENSP00000416578.2		P20929-3

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39680

AN:

151960

Hom.:

6197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0820

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.269

GnomAD2 exomes

AF:

0.301

AC:

71191

AN:

236906

AF XY:

0.299

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.262

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.350

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.335

AC:

482412

AN:

1441762

Hom.:

83752

Cov.:

AF XY:

0.330

AC XY:

236330

AN XY:

715206

show subpopulations

African (AFR)

AF:

0.0712

AC:

2344

AN:

32914

American (AMR)

AF:

0.316

AC:

13645

AN:

43222

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

6139

AN:

24964

East Asian (EAS)

AF:

0.279

AC:

11023

AN:

39476

South Asian (SAS)

AF:

0.202

AC:

16892

AN:

83758

European-Finnish (FIN)

AF:

0.350

AC:

18461

AN:

52684

Middle Eastern (MID)

AF:

0.290

AC:

1639

AN:

5646

European-Non Finnish (NFE)

AF:

0.358

AC:

394053

AN:

1099636

Other (OTH)

AF:

0.306

AC:

18216

AN:

59462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

16874

33748

50622

67496

84370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12498

24996

37494

49992

62490

<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:

0.261

AC:

39690

AN:

152078

Hom.:

6203

Cov.:

AF XY:

0.261

AC XY:

19380

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0819

AC:

3400

AN:

41516

American (AMR)

AF:

0.287

AC:

4380

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

827

AN:

3470

East Asian (EAS)

AF:

0.257

AC:

1328

AN:

5174

South Asian (SAS)

AF:

0.202

AC:

975

AN:

4816

European-Finnish (FIN)

AF:

0.360

AC:

3798

AN:

10552

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24205

AN:

67982

Other (OTH)

AF:

0.266

AC:

561

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1387

2774

4162

5549

6936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.304

Hom.:

1366

Bravo

AF:

0.248

Asia WGS

AF:

0.228

AC:

793

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

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.56

PhyloP100

-0.89

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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