dbSNP rs10491056: NEBL:c.1671+9T>C (chr10-20831187-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006393.3(NEBL):c.1671+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,590,794 control chromosomes in the GnomAD database, including 112,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14810 hom., cov: 31)

Exomes 𝑓: 0.36 ( 97251 hom. )

Consequence

NEBL
NM_006393.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.250

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-20831187-A-G is Benign according to our data. Variant chr10-20831187-A-G is described in ClinVar as [Benign]. Clinvar id is 45484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_006393.3 link	c.1671+9T>C		intron_variant	Intron 16 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.1671+9T>C		intron_variant	Intron 16 of 27	1	NM_006393.3	ENSP00000366326.4		O76041-1

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64458

AN:

151818

Hom.:

14779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.606

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.537

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.430

GnomAD3 exomes

AF:

0.386

AC:

96307

AN:

249204

Hom.:

19836

AF XY:

0.387

AC XY:

52135

AN XY:

134724

show subpopulations

Gnomad AFR exome

AF:

0.610

Gnomad AMR exome

AF:

0.314

Gnomad ASJ exome

AF:

0.418

Gnomad EAS exome

AF:

0.562

Gnomad SAS exome

AF:

0.432

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.373

GnomAD4 exome

AF:

0.362

AC:

520706

AN:

1438858

Hom.:

97251

Cov.:

AF XY:

0.363

AC XY:

260488

AN XY:

717304

show subpopulations

Gnomad4 AFR exome

AF:

0.620

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.430

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.346

Gnomad4 OTH exome

AF:

0.397

GnomAD4 genome

AF:

0.425

AC:

64543

AN:

151936

Hom.:

14810

Cov.:

AF XY:

0.420

AC XY:

31221

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.606

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.431

Gnomad4 EAS

AF:

0.537

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.350

Gnomad4 OTH

AF:

0.428

Alfa

AF:

0.371

Hom.:

23581

Bravo

AF:

0.441

Asia WGS

AF:

0.467

AC:

1623

AN:

3478

EpiCase

AF:

0.374

EpiControl

AF:

0.378

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 22, 2013

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. -

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 19, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.1671+9T>C in Intron 16 of NEBL: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and has been identified in 40.3% (1504/3736) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington .edu/EVS; dbSNP rs10491056). -

NEBL-related disorder

Benign:1

May 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary dilated cardiomyopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.79

CADD

Benign

5.3

DANN

Benign

0.58

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

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