dbSNP rs67179: NEBL:c.165-9762T>C (chr10-21029963-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000417816.2(NEBL):c.165-9762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 541,278 control chromosomes in the GnomAD database, including 107,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 26696 hom., cov: 31)

Exomes 𝑓: 0.64 ( 80342 hom. )

Consequence

NEBL
ENST00000417816.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0630

Publications

2 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:

EIF4BP2 (HGNC:37935): (eukaryotic translation initiation factor 4B pseudogene 2)

EIF4BP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
EIF4BP2		n.21029963A>G	intragenic_variant
NEBL	NM_001377322.1 link	c.165-9762T>C	intron_variant	Intron 2 of 7	NP_001364251.1
NEBL	NM_213569.2 link	c.165-9762T>C	intron_variant	Intron 2 of 6	NP_998734.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
NEBL	ENST00000417816.2 link	c.165-9762T>C	intron_variant	Intron 2 of 6	1	ENSP00000393896.2
EIF4BP2	ENST00000416702.1 link	n.965A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
NEBL	ENST00000675114.1 link	n.373-9762T>C	intron_variant	Intron 4 of 8

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89702

AN:

151692

Hom.:

26666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.529

Gnomad EAS

AF:

0.725

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.648

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.613

Gnomad OTH

AF:

0.594

GnomAD4 exome

AF:

0.640

AC:

249387

AN:

389470

Hom.:

80342

Cov.:

AF XY:

0.641

AC XY:

135531

AN XY:

211564

show subpopulations

African (AFR)

AF:

0.511

AC:

5681

AN:

11114

American (AMR)

AF:

0.681

AC:

15620

AN:

22924

Ashkenazi Jewish (ASJ)

AF:

0.549

AC:

5340

AN:

9734

East Asian (EAS)

AF:

0.744

AC:

15235

AN:

20478

South Asian (SAS)

AF:

0.668

AC:

33049

AN:

49482

European-Finnish (FIN)

AF:

0.670

AC:

24552

AN:

36636

Middle Eastern (MID)

AF:

0.578

AC:

775

AN:

1340

European-Non Finnish (NFE)

AF:

0.627

AC:

136467

AN:

217746

Other (OTH)

AF:

0.633

AC:

12668

AN:

20016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

4261

8523

12784

17046

21307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

924

1848

2772

3696

4620

<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:

0.591

AC:

89785

AN:

151808

Hom.:

26696

Cov.:

AF XY:

0.594

AC XY:

44066

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.511

AC:

21107

AN:

41280

American (AMR)

AF:

0.624

AC:

9532

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

1834

AN:

3468

East Asian (EAS)

AF:

0.725

AC:

3739

AN:

5154

South Asian (SAS)

AF:

0.668

AC:

3215

AN:

4816

European-Finnish (FIN)

AF:

0.648

AC:

6839

AN:

10550

Middle Eastern (MID)

AF:

0.531

AC:

155

AN:

292

European-Non Finnish (NFE)

AF:

0.613

AC:

41654

AN:

67952

Other (OTH)

AF:

0.594

AC:

1254

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1900

3800

5700

7600

9500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.486

Hom.:

1510

Bravo

AF:

0.585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.9

(source)

DANN

Benign

0.46

PhyloP100

0.063

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over