Variant chr2-151560550-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001164507.2(NEB):c.19314+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6392 hom., cov: 27)

Exomes 𝑓: 0.26 ( 45134 hom. )

Failed GnomAD Quality Control

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.447

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 -12 ACMG points.

BP4

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

BP6

Variant 2-151560550-G-A is Benign according to our data. Variant chr2-151560550-G-A is described in ClinVar as [Benign]. Clinvar id is 257779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151560550-G-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEB	NM_001164507.2 linkuse as main transcript	c.19314+42C>T		intron_variant		ENST00000427231.7
NEB	NM_001164508.2 linkuse as main transcript	c.19314+42C>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.19314+42C>T		intron_variant		5	NM_001164508.2	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.19314+42C>T		intron_variant		5	NM_001164507.2	A2	P20929-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

42660

AN:

150794

Hom.:

6387

Cov.:

FAILED QC

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.295

AC:

49242

AN:

166744

Hom.:

7800

AF XY:

0.286

AC XY:

25207

AN XY:

88240

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.283

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.259

AC:

332874

AN:

1284046

Hom.:

45134

Cov.:

AF XY:

0.257

AC XY:

164443

AN XY:

640206

show subpopulations

Gnomad4 AFR exome

AF:

0.313

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.357

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.283

AC:

42694

AN:

150912

Hom.:

6392

Cov.:

AF XY:

0.284

AC XY:

20920

AN XY:

73662

show subpopulations

Gnomad4 AFR

AF:

0.306

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.267

Hom.:

942

Bravo

AF:

0.297

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

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

-0.82

CADD

Benign

6.1

DANN

Benign

0.74

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