Variant rs2288201 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.20158-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,421,254 control chromosomes in the GnomAD database, including 288,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30717 hom., cov: 31)

Exomes 𝑓: 0.63 ( 257510 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.125

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-151547780-C-T is Benign according to our data. Variant chr2-151547780-C-T is described in ClinVar as [Benign]. Clinvar id is 257783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151547780-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 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.20158-42G>A		intron_variant		ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 linkuse as main transcript	c.20158-42G>A		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.20158-42G>A		intron_variant		5	NM_001164508.2	ENSP00000380505	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.20158-42G>A		intron_variant		5	NM_001164507.2	ENSP00000416578	A2	P20929-3

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96048

AN:

151646

Hom.:

30670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.716

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.771

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.676

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.639

GnomAD3 exomes

AF:

0.642

AC:

133760

AN:

208318

Hom.:

43444

AF XY:

0.631

AC XY:

70575

AN XY:

111840

show subpopulations

Gnomad AFR exome

AF:

0.610

Gnomad AMR exome

AF:

0.752

Gnomad ASJ exome

AF:

0.540

Gnomad EAS exome

AF:

0.777

Gnomad SAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.665

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.649

GnomAD4 exome

AF:

0.635

AC:

805915

AN:

1269490

Hom.:

257510

Cov.:

AF XY:

0.629

AC XY:

400223

AN XY:

636424

show subpopulations

Gnomad4 AFR exome

AF:

0.611

Gnomad4 AMR exome

AF:

0.741

Gnomad4 ASJ exome

AF:

0.532

Gnomad4 EAS exome

AF:

0.793

Gnomad4 SAS exome

AF:

0.491

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.638

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.634

AC:

96156

AN:

151764

Hom.:

30717

Cov.:

AF XY:

0.636

AC XY:

47186

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.604

Gnomad4 AMR

AF:

0.716

Gnomad4 ASJ

AF:

0.532

Gnomad4 EAS

AF:

0.770

Gnomad4 SAS

AF:

0.502

Gnomad4 FIN

AF:

0.676

Gnomad4 NFE

AF:

0.632

Gnomad4 OTH

AF:

0.644

Alfa

AF:

0.632

Hom.:

5644

Bravo

AF:

0.640

Asia WGS

AF:

0.630

AC:

2193

AN:

3478

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

-0.90

CADD

Benign

1.6

DANN

Benign

0.71

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