rs923819811

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006393.3(NEBL):c.259-13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,402,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

NEBL
NM_006393.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.18

Publications

0 publications found

Variant links:

Genes affected

NEBL (HGNC:16932): (nebulette) This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

NEBL Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

NEBL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-20888220-A-C is Benign according to our data. Variant chr10-20888220-A-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 506239.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_006393.3 link	c.259-13T>G		intron_variant	Intron 3 of 27	ENST00000377122.9	NP_006384.1	O76041-1Q59FZ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000377122.9 link	c.259-13T>G		intron_variant	Intron 3 of 27	1	NM_006393.3	ENSP00000366326.4		O76041-1

Frequencies

GnomAD3 genomes

AF:

0.0000732

AC:

AN:

95648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

160850

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000887

Gnomad AMR exome

AF:

0.0000466

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000995

AC:

AN:

1307136

Hom.:

Cov.:

AF XY:

0.00000759

AC XY:

AN XY:

658598

show subpopulations

African (AFR)

AF:

0.000166

AC:

AN:

30128

American (AMR)

AF:

0.000114

AC:

AN:

43886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25112

East Asian (EAS)

AF:

0.00

AC:

AN:

38880

South Asian (SAS)

AF:

0.00

AC:

AN:

81048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

974338

Other (OTH)

AF:

0.0000544

AC:

AN:

55196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000732

AC:

AN:

95648

Hom.:

Cov.:

AF XY:

0.0000432

AC XY:

AN XY:

46246

show subpopulations

African (AFR)

AF:

0.000164

AC:

AN:

30452

American (AMR)

AF:

0.000223

AC:

AN:

8968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2550

East Asian (EAS)

AF:

0.00

AC:

AN:

4280

South Asian (SAS)

AF:

0.00

AC:

AN:

3018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

39598

Other (OTH)

AF:

0.00

AC:

AN:

1328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000756

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant classified as Uncertain Significance - Favor Benign. The c.259-13T>G var iant in NEBL has not been previously reported in individuals with cardiomyopathy . This variant has been identified in 2/17494 African chromosomes and 1/21470 La tin chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadi nstitute.org; dnSNP rs 923819811). This variant is located in the 5' splice regi on. Computational tools do not suggest an impact to splicing. However, this info rmation is not predictive enough to rule out pathogenicity. In summary, the cli nical significance of the c.259-13T>G variant is uncertain. ACMG/AMP Criteria ap plied: PM2; BP4. -

Primary dilated cardiomyopathy

Benign:1

May 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.85

CADD

Benign

1.8

(source)

DANN

Benign

0.48

PhyloP100

1.2

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over