10-20835499-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006393.3(NEBL):c.1449+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,578,316 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

NEBL
NM_006393.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.63

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 10-20835499-C-T is Benign according to our data. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-20835499-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 45480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_006393.3 link	c.1449+14G>A		intron_variant	Intron 14 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.1449+14G>A		intron_variant	Intron 14 of 27	1	NM_006393.3	ENSP00000366326.4		O76041-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000128

AC:

AN:

249402

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000198

AC:

283

AN:

1426132

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

136

AN XY:

711714

show subpopulations

African (AFR)

AF:

0.0000612

AC:

AN:

32676

American (AMR)

AF:

0.00

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25948

East Asian (EAS)

AF:

0.0000759

AC:

AN:

39522

South Asian (SAS)

AF:

0.00

AC:

AN:

85624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.000252

AC:

273

AN:

1082330

Other (OTH)

AF:

0.0000674

AC:

AN:

59382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000125

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000982

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 19, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1449+14G>A in intron 14 of NEBL: This variant is not expected to have clinical s ignificance because it is not located within the splice consensus sequence. It h as been identified in 1/7020 European American chromosomes from a broad populati on by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). 14 49+14G>A in intron 14 of NEBL (allele frequency= 1/7020) ** -

Apr 13, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Primary dilated cardiomyopathy

Benign:1

Jan 13, 2025

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

-0.92

CADD

Benign

0.0090

(source)

DANN

Benign

0.52

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(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

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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