Variant rs16830136 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.22800+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,451,234 control chromosomes in the GnomAD database, including 272,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26967 hom., cov: 32)

Exomes 𝑓: 0.61 ( 245497 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.74

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:

RIF1 (HGNC:):

RIF1 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=-0.87).

BP6

Variant 2-151518286-G-A is Benign according to our data. Variant chr2-151518286-G-A is described in ClinVar as [Benign]. Clinvar id is 257792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151518286-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.685 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.22800+32C>T		intron_variant		ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 linkuse as main transcript	c.22800+32C>T		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.22800+32C>T		intron_variant		5	NM_001164508.2	ENSP00000380505	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.22800+32C>T		intron_variant		5	NM_001164507.2	ENSP00000416578	A2	P20929-3

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89787

AN:

151888

Hom.:

26944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.643

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.588

GnomAD3 exomes

AF:

0.598

AC:

148937

AN:

248920

Hom.:

45729

AF XY:

0.586

AC XY:

79158

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.516

Gnomad AMR exome

AF:

0.732

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.580

Gnomad SAS exome

AF:

0.409

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.616

GnomAD4 exome

AF:

0.611

AC:

793734

AN:

1299228

Hom.:

245497

Cov.:

AF XY:

0.604

AC XY:

395239

AN XY:

654820

show subpopulations

Gnomad4 AFR exome

AF:

0.519

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.521

Gnomad4 EAS exome

AF:

0.628

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.641

Gnomad4 NFE exome

AF:

0.626

Gnomad4 OTH exome

AF:

0.601

GnomAD4 genome

AF:

0.591

AC:

89850

AN:

152006

Hom.:

26967

Cov.:

AF XY:

0.592

AC XY:

43978

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.696

Gnomad4 ASJ

AF:

0.511

Gnomad4 EAS

AF:

0.583

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.643

Gnomad4 NFE

AF:

0.625

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.610

Hom.:

5237

Bravo

AF:

0.597

Asia WGS

AF:

0.463

AC:

1613

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

-0.87

CADD

Benign

0.021

DANN

Benign

0.47

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