Genetic Variant NEBL:c.*221A>G (chr10-20785526-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006393.3(NEBL):c.*221A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 578,660 control chromosomes in the GnomAD database, including 24,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5346 hom., cov: 32)

Exomes 𝑓: 0.30 ( 19577 hom. )

Consequence

NEBL
NM_006393.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.25

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 10-20785526-T-C is Benign according to our data. Variant chr10-20785526-T-C is described in ClinVar as [Benign]. Clinvar id is 1244881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_006393.3 link	c.*221A>G		3_prime_UTR_variant	Exon 28 of 28	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.*221A>G		3_prime_UTR_variant	Exon 28 of 28	1	NM_006393.3	ENSP00000366326.4		O76041-1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39016

AN:

151930

Hom.:

5342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.278

GnomAD4 exome

AF:

0.296

AC:

126144

AN:

426614

Hom.:

19577

Cov.:

AF XY:

0.301

AC XY:

68318

AN XY:

227124

show subpopulations

African (AFR)

AF:

0.179

AC:

2131

AN:

11902

American (AMR)

AF:

0.240

AC:

4588

AN:

19100

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

4004

AN:

12898

East Asian (EAS)

AF:

0.371

AC:

10316

AN:

27826

South Asian (SAS)

AF:

0.378

AC:

17033

AN:

45018

European-Finnish (FIN)

AF:

0.208

AC:

5339

AN:

25698

Middle Eastern (MID)

AF:

0.334

AC:

619

AN:

1852

European-Non Finnish (NFE)

AF:

0.290

AC:

74943

AN:

258088

Other (OTH)

AF:

0.296

AC:

7171

AN:

24232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4293

8586

12879

17172

21465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.257

AC:

39037

AN:

152046

Hom.:

5346

Cov.:

AF XY:

0.254

AC XY:

18892

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.182

AC:

7568

AN:

41472

American (AMR)

AF:

0.245

AC:

3740

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1081

AN:

3470

East Asian (EAS)

AF:

0.429

AC:

2212

AN:

5162

South Asian (SAS)

AF:

0.385

AC:

1857

AN:

4820

European-Finnish (FIN)

AF:

0.202

AC:

2137

AN:

10590

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.287

AC:

19506

AN:

67966

Other (OTH)

AF:

0.277

AC:

582

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1447

2894

4340

5787

7234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.283

Hom.:

18524

Bravo

AF:

0.256

Asia WGS

AF:

0.391

AC:

1359

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-20785526-T-C

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