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

Publications

11 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=-0.79).

BP6

Variant 10-20831187-A-G is Benign according to our data. Variant chr10-20831187-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006393.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEBL	NM_006393.3	MANE Select	c.1671+9T>C	intron	N/A	NP_006384.1	O76041-1
NEBL	NM_001377322.1		c.358-18247T>C	intron	N/A	NP_001364251.1
NEBL	NM_213569.2		c.358-18247T>C	intron	N/A	NP_998734.1	Q59FZ8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEBL	ENST00000377122.9	TSL:1 MANE Select	c.1671+9T>C	intron	N/A	ENSP00000366326.4	O76041-1
NEBL	ENST00000417816.2	TSL:1	c.358-18247T>C	intron	N/A	ENSP00000393896.2	O76041-2
NEBL	ENST00000493005.5	TSL:1	n.271+9T>C	intron	N/A

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

GnomAD2 exomes

AF:

0.386

AC:

96307

AN:

249204

AF XY:

0.387

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 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

African (AFR)

AF:

0.620

AC:

20439

AN:

32958

American (AMR)

AF:

0.320

AC:

14261

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

10862

AN:

26020

East Asian (EAS)

AF:

0.495

AC:

19597

AN:

39560

South Asian (SAS)

AF:

0.430

AC:

36859

AN:

85790

European-Finnish (FIN)

AF:

0.280

AC:

14832

AN:

52896

Middle Eastern (MID)

AF:

0.513

AC:

2928

AN:

5704

European-Non Finnish (NFE)

AF:

0.346

AC:

377211

AN:

1091634

Other (OTH)

AF:

0.397

AC:

23717

AN:

59672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

16005

32010

48015

64020

80025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12192

24384

36576

48768

60960

<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:

0.425

AC:

64543

AN:

151936

Hom.:

14810

Cov.:

AF XY:

0.420

AC XY:

31221

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.606

AC:

25107

AN:

41410

American (AMR)

AF:

0.340

AC:

5183

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

1498

AN:

3472

East Asian (EAS)

AF:

0.537

AC:

2769

AN:

5158

South Asian (SAS)

AF:

0.430

AC:

2071

AN:

4816

European-Finnish (FIN)

AF:

0.270

AC:

2856

AN:

10566

Middle Eastern (MID)

AF:

0.462

AC:

135

AN:

292

European-Non Finnish (NFE)

AF:

0.350

AC:

23762

AN:

67954

Other (OTH)

AF:

0.428

AC:

902

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1768

3536

5304

7072

8840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.381

Hom.:

34489

Bravo

AF:

0.441

Asia WGS

AF:

0.467

AC:

1623

AN:

3478

EpiCase

AF:

0.374

EpiControl

AF:

0.378

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

NEBL-related disorder (1)

not provided (1)

Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.3

(source)

DANN

Benign

0.58

PhyloP100

0.25

Mutation Taster

=99/1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over