dbSNP rs57918610: NEBL:c.259-10_259-8delTTT (chr10-20888214-GAAA-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006393.3(NEBL):c.259-10_259-8delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,404,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

NEBL
NM_006393.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.175

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_006393.3 link	c.259-10_259-8delTTT		splice_region_variant, intron_variant	Intron 3 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.259-10_259-8delTTT		splice_region_variant, intron_variant	Intron 3 of 27	1	NM_006393.3	ENSP00000366326.4		O76041-1

Frequencies

GnomAD3 genomes

AF:

0.00000882

AC:

AN:

113352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000200

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000232

AC:

AN:

1291166

Hom.:

AF XY:

0.00000155

AC XY:

AN XY:

646958

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29110

American (AMR)

AF:

0.00

AC:

AN:

41056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23972

East Asian (EAS)

AF:

0.00

AC:

AN:

37128

South Asian (SAS)

AF:

0.00

AC:

AN:

78234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5250

European-Non Finnish (NFE)

AF:

0.00000309

AC:

AN:

972416

Other (OTH)

AF:

0.00

AC:

AN:

53590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000882

AC:

AN:

113352

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

54536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

34124

American (AMR)

AF:

0.00

AC:

AN:

10272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2902

East Asian (EAS)

AF:

0.00

AC:

AN:

4514

South Asian (SAS)

AF:

0.00

AC:

AN:

3400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0000200

AC:

AN:

50038

Other (OTH)

AF:

0.00

AC:

AN:

1536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.17

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over