Variant rs4364020 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001164507.2(NEB):c.19101+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,573,978 control chromosomes in the GnomAD database, including 1,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.055 ( 647 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1225 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0660

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-151561167-G-A is Benign according to our data. Variant chr2-151561167-G-A is described in ClinVar as [Benign]. Clinvar id is 257777.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEB	NM_001164507.2 linkuse as main transcript	c.19101+41C>T		intron_variant		ENST00000427231.7
NEB	NM_001164508.2 linkuse as main transcript	c.19101+41C>T		intron_variant		ENST00000397345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEB	ENST00000397345.8 linkuse as main transcript	c.19101+41C>T		intron_variant		5	NM_001164508.2	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.19101+41C>T		intron_variant		5	NM_001164507.2	A2	P20929-3

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8355

AN:

152066

Hom.:

635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0231

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0767

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00221

Gnomad OTH

AF:

0.0517

GnomAD3 exomes

AF:

0.0336

AC:

7473

AN:

222124

Hom.:

445

AF XY:

0.0333

AC XY:

3987

AN XY:

119864

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0325

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.0666

Gnomad FIN exome

AF:

0.000149

Gnomad NFE exome

AF:

0.00231

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0151

AC:

21531

AN:

1421794

Hom.:

1225

Cov.:

AF XY:

0.0163

AC XY:

11554

AN XY:

707032

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.0679

Gnomad4 FIN exome

AF:

0.000344

Gnomad4 NFE exome

AF:

0.00167

Gnomad4 OTH exome

AF:

0.0295

GnomAD4 genome

AF:

0.0552

AC:

8398

AN:

152184

Hom.:

647

Cov.:

AF XY:

0.0552

AC XY:

4108

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.0231

Gnomad4 ASJ

AF:

0.0320

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.0774

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00221

Gnomad4 OTH

AF:

0.0611

Alfa

AF:

0.00748

Hom.:

Bravo

AF:

0.0613

Asia WGS

AF:

0.139

AC:

482

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.28

DANN

Benign

0.54

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