Variant rs6433569 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_001164507.2(NEB):c.1674+30T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,526,238 control chromosomes in the GnomAD database, including 468,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 35798 hom., cov: 32)

Exomes 𝑓: 0.78 ( 432730 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.152

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 -20 ACMG points.

BP4

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

BP6

Variant 2-151695548-A-C is Benign according to our data. Variant chr2-151695548-A-C is described in ClinVar as [Benign]. Clinvar id is 257767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151695548-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.816 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.1674+30T>G		intron_variant		ENST00000427231.7
NEB	NM_001164508.2 linkuse as main transcript	c.1674+30T>G		intron_variant		ENST00000397345.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
NEB	ENST00000397345.8 linkuse as main transcript	c.1674+30T>G	intron_variant	5	NM_001164508.2	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.1674+30T>G	intron_variant	5	NM_001164507.2	A2	P20929-3
NEB	ENST00000489048.1 linkuse as main transcript	n.573+30T>G	intron_variant, non_coding_transcript_variant	1
NEB	ENST00000409198.5 linkuse as main transcript	c.1674+30T>G	intron_variant	5			P20929-4

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95503

AN:

152034

Hom.:

35795

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.815

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.822

Gnomad OTH

AF:

0.679

GnomAD3 exomes

AF:

0.733

AC:

175634

AN:

239766

Hom.:

68488

AF XY:

0.737

AC XY:

95681

AN XY:

129774

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.849

Gnomad ASJ exome

AF:

0.734

Gnomad EAS exome

AF:

0.412

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.851

Gnomad NFE exome

AF:

0.824

Gnomad OTH exome

AF:

0.768

GnomAD4 exome

AF:

0.783

AC:

1075274

AN:

1374086

Hom.:

432730

Cov.:

AF XY:

0.780

AC XY:

536378

AN XY:

687496

show subpopulations

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.840

Gnomad4 ASJ exome

AF:

0.735

Gnomad4 EAS exome

AF:

0.385

Gnomad4 SAS exome

AF:

0.646

Gnomad4 FIN exome

AF:

0.849

Gnomad4 NFE exome

AF:

0.824

Gnomad4 OTH exome

AF:

0.738

GnomAD4 genome

AF:

0.628

AC:

95499

AN:

152152

Hom.:

35798

Cov.:

AF XY:

0.633

AC XY:

47053

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.783

Gnomad4 ASJ

AF:

0.726

Gnomad4 EAS

AF:

0.394

Gnomad4 SAS

AF:

0.641

Gnomad4 FIN

AF:

0.859

Gnomad4 NFE

AF:

0.822

Gnomad4 OTH

AF:

0.671

Alfa

AF:

0.643

Hom.:

7322

Bravo

AF:

0.605

Asia WGS

AF:

0.446

AC:

1553

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Nemaline myopathy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Arthrogryposis multiplex congenita 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.8

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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