Variant 10-20819448-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006393.3(NEBL):c.2031G>A(p.Arg677=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,613,702 control chromosomes in the GnomAD database, including 66,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4653 hom., cov: 32)

Exomes 𝑓: 0.28 ( 61714 hom. )

Consequence

NEBL
NM_006393.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0920

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 10-20819448-C-T is Benign according to our data. Variant chr10-20819448-C-T is described in ClinVar as [Benign]. Clinvar id is 45489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.092 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEBL	NM_006393.3 linkuse as main transcript	c.2031G>A	p.Arg677=	synonymous_variant	20/28	ENST00000377122.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEBL	ENST00000377122.9 linkuse as main transcript	c.2031G>A	p.Arg677=	synonymous_variant	20/28	1	NM_006393.3		O76041-1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33874

AN:

151958

Hom.:

4653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0642

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.247

AC:

62107

AN:

251314

Hom.:

8586

AF XY:

0.250

AC XY:

33907

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0627

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.298

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.284

AC:

414474

AN:

1461626

Hom.:

61714

Cov.:

AF XY:

0.281

AC XY:

204568

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.172

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.375

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.223

AC:

33870

AN:

152076

Hom.:

4653

Cov.:

AF XY:

0.226

AC XY:

16784

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0641

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.226

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.266

Hom.:

6848

Bravo

AF:

0.201

Asia WGS

AF:

0.182

AC:

635

AN:

3478

EpiCase

AF:

0.277

EpiControl

AF:

0.271

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 19, 2012	p.Arg677Arg in Exon 20 of NEBL: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence and has been identified in 29.6% (2079/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1006363). -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Oct 22, 2015	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Primary dilated cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over