Genetic Variant NEBL:c.-229_-224dupGAGCCG (chr10-21174056-T-TCGGCTC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001377322.1(NEBL):c.-229_-224dupGAGCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000808 in 1,114,064 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

NEBL
NM_001377322.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.187

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 links:

NEBL-AS1 (HGNC:44899): (NEBL antisense RNA 1)

NEBL-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377322.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
NEBL	NM_001377322.1	c.-229_-224dupGAGCCG	5_prime_UTR	Exon 1 of 8	NP_001364251.1
NEBL	NM_213569.2	c.-229_-224dupGAGCCG	5_prime_UTR	Exon 1 of 7	NP_998734.1	Q59FZ8
NEBL	NM_001377324.1	c.-387_-382dupGAGCCG	5_prime_UTR	Exon 1 of 7	NP_001364253.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEBL	ENST00000417816.2	TSL:1	c.-229_-224dupGAGCCG	5_prime_UTR	Exon 1 of 7	ENSP00000393896.2	O76041-2
NEBL-AS1	ENST00000439097.2	TSL:2	n.61_66dupGCTCCG	non_coding_transcript_exon	Exon 1 of 2
NEBL	ENST00000675700.1		n.92+778_92+783dupGAGCCG	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000924

AC:

AN:

151540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000482

GnomAD4 exome

AF:

0.0000790

AC:

AN:

962524

Hom.:

Cov.:

AF XY:

0.0000573

AC XY:

AN XY:

453448

show subpopulations

African (AFR)

AF:

0.0000526

AC:

AN:

19020

American (AMR)

AF:

0.00

AC:

AN:

4540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9234

East Asian (EAS)

AF:

0.0000738

AC:

AN:

13552

South Asian (SAS)

AF:

0.00

AC:

AN:

18354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2262

European-Non Finnish (NFE)

AF:

0.0000849

AC:

AN:

847678

Other (OTH)

AF:

0.0000564

AC:

AN:

35436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.0000924

AC:

AN:

151540

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

73986

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41280

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67856

Other (OTH)

AF:

0.000482

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.19

Splicing

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

Publications

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10-21174056-TCGGCTC-TCGGCTCCGGCTC

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