Variant chr2-151513538-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001164508.2(NEB):c.23241+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,424,300 control chromosomes in the GnomAD database, including 766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 79 hom., cov: 32)

Exomes 𝑓: 0.011 ( 687 hom. )

Consequence

NEB
NM_001164508.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0610

Variant links:

Genes affected

NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

NEB links:

RIF1 (HGNC:):

RIF1 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=-0.86).

BP6

Variant 2-151513538-A-G is Benign according to our data. Variant chr2-151513538-A-G is described in ClinVar as [Benign]. Clinvar id is 257798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEB	NM_001164507.2 linkuse as main transcript	c.23241+42T>C		intron_variant		ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 linkuse as main transcript	c.23241+42T>C		intron_variant		ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEB	ENST00000397345.8 linkuse as main transcript	c.23241+42T>C		intron_variant		5	NM_001164508.2	ENSP00000380505	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.23241+42T>C		intron_variant		5	NM_001164507.2	ENSP00000416578	A2	P20929-3

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2227

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0755

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00195

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0233

AC:

4180

AN:

179392

Hom.:

206

AF XY:

0.0259

AC XY:

2456

AN XY:

94820

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.0315

Gnomad EAS exome

AF:

0.140

Gnomad SAS exome

AF:

0.0675

Gnomad FIN exome

AF:

0.0000559

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0111

AC:

14144

AN:

1272012

Hom.:

687

Cov.:

AF XY:

0.0129

AC XY:

8209

AN XY:

635660

show subpopulations

Gnomad4 AFR exome

AF:

0.0169

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.0311

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.0679

Gnomad4 FIN exome

AF:

0.000277

Gnomad4 NFE exome

AF:

0.00147

Gnomad4 OTH exome

AF:

0.0191

GnomAD4 genome

AF:

0.0148

AC:

2261

AN:

152288

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1204

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.00752

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.0764

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00196

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.00907

Hom.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.124

AC:

428

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.8

DANN

Benign

0.63

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