rs141707642

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001377322.1(NEBL):c.-7C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,610,848 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 89 hom. )

Consequence

NEBL
NM_001377322.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0820

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 10-21173840-G-A is Benign according to our data. Variant chr10-21173840-G-A is described in ClinVar as [Benign]. Clinvar id is 48638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1656/151970) while in subpopulation AFR AF= 0.0255 (1057/41506). AF 95% confidence interval is 0.0242. There are 14 homozygotes in gnomad4. There are 799 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
NEBL	NM_001377322.1 link	c.-7C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	NP_001364251.1
NEBL	NM_213569.2 link	c.-7C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	NP_998734.1	O76041-2Q59FZ8
NEBL	NM_001377324.1 link	c.-165C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	NP_001364253.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NEBL	ENST00000417816.2 link	c.-7C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	ENSP00000393896.2	O76041-2
NEBL	ENST00000417816.2 link	c.-7C>T	5_prime_UTR_variant	Exon 1 of 7	1	ENSP00000393896.2	O76041-2
NEBL	ENST00000675747.1 link	n.54C>T	non_coding_transcript_exon_variant	Exon 1 of 28

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1655

AN:

151856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0249

Gnomad FIN

AF:

0.00520

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00461

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00714

AC:

1736

AN:

243110

Hom.:

AF XY:

0.00775

AC XY:

1029

AN XY:

132740

show subpopulations

Gnomad AFR exome

AF:

0.0256

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.00252

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0203

Gnomad FIN exome

AF:

0.00373

Gnomad NFE exome

AF:

0.00475

Gnomad OTH exome

AF:

0.00517

GnomAD4 exome

AF:

0.00601

AC:

8762

AN:

1458878

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

4657

AN XY:

725812

show subpopulations

Gnomad4 AFR exome

AF:

0.0278

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.00261

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.00355

Gnomad4 NFE exome

AF:

0.00467

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.0109

AC:

1656

AN:

151970

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

799

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.0255

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0248

Gnomad4 FIN

AF:

0.00520

Gnomad4 NFE

AF:

0.00461

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00302

Hom.:

Bravo

AF:

0.0112

EpiCase

AF:

0.00496

EpiControl

AF:

0.00409

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 19, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.-7C>T in Exon 01 of NEBL: This variant is not expected to have clinical signif icance because it has been identified in 2.1% (79/3736) of African American chro mosomes from a broad population by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu/EVS; dbSNP rs141707642). -

NEBL-related disorder

Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

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

-0.66

CADD

Benign

DANN

Benign

0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over