Variant chr2-151666042-T-C 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.5031+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,544,304 control chromosomes in the GnomAD database, including 22,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3947 hom., cov: 32)

Exomes 𝑓: 0.14 ( 18486 hom. )

Consequence

NEB
NM_001164508.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.310

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=-0.91).

BP6

Variant 2-151666042-T-C is Benign according to our data. Variant chr2-151666042-T-C is described in ClinVar as [Benign]. Clinvar id is 257816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151666042-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEB	NM_001164507.2 link	c.5031+48A>G		intron_variant		ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 link	c.5031+48A>G		intron_variant		ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NEB	ENST00000397345.8 link	c.5031+48A>G	intron_variant	5	NM_001164508.2	ENSP00000380505.3	P20929-2
NEB	ENST00000427231.7 link	c.5031+48A>G	intron_variant	5	NM_001164507.2	ENSP00000416578.2	P20929-3
NEB	ENST00000409198.5 link	c.5031+48A>G	intron_variant	5		ENSP00000386259.1	P20929-4

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29308

AN:

151988

Hom.:

3925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.493

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.177

AC:

37585

AN:

212230

Hom.:

4920

AF XY:

0.177

AC XY:

19979

AN XY:

112968

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.481

Gnomad SAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.136

AC:

188644

AN:

1392198

Hom.:

18486

Cov.:

AF XY:

0.139

AC XY:

95102

AN XY:

686184

show subpopulations

Gnomad4 AFR exome

AF:

0.357

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.514

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.193

AC:

29378

AN:

152106

Hom.:

3947

Cov.:

AF XY:

0.195

AC XY:

14482

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.493

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.142

Hom.:

403

Bravo

AF:

0.199

Asia WGS

AF:

0.414

AC:

1434

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

-0.91

CADD

Benign

9.5

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