rs6717213

Positions:

chr2-151619616-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001164507.2(NEB):c.10707G>A(p.Lys3569=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0391 in 1,613,874 control chromosomes in the GnomAD database, including 3,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 1073 hom., cov: 31)

Exomes 𝑓: 0.034 ( 2567 hom. )

Consequence

NEB
NM_001164507.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 4.97

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 2-151619616-C-T is Benign according to our data. Variant chr2-151619616-C-T is described in ClinVar as [Benign]. Clinvar id is 129762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 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.10707G>A	p.Lys3569=	synonymous_variant	73/182	ENST00000427231.7
NEB	NM_001164508.2 linkuse as main transcript	c.10707G>A	p.Lys3569=	synonymous_variant	73/182	ENST00000397345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEB	ENST00000397345.8 linkuse as main transcript	c.10707G>A	p.Lys3569=	synonymous_variant	73/182	5	NM_001164508.2	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.10707G>A	p.Lys3569=	synonymous_variant	73/182	5	NM_001164507.2	A2	P20929-3
NEB	ENST00000409198.5 linkuse as main transcript	c.9978G>A	p.Lys3326=	synonymous_variant	70/150	5			P20929-4

Frequencies

GnomAD3 genomes

AF:

0.0834

AC:

12685

AN:

152090

Hom.:

1058

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0456

Gnomad ASJ

AF:

0.0639

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0778

GnomAD3 exomes

AF:

0.0556

AC:

13836

AN:

248946

Hom.:

920

AF XY:

0.0561

AC XY:

7576

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.0214

Gnomad ASJ exome

AF:

0.0612

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.0178

Gnomad OTH exome

AF:

0.0409

GnomAD4 exome

AF:

0.0344

AC:

50338

AN:

1461666

Hom.:

2567

Cov.:

AF XY:

0.0363

AC XY:

26422

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0640

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.0177

Gnomad4 OTH exome

AF:

0.0531

GnomAD4 genome

AF:

0.0838

AC:

12756

AN:

152208

Hom.:

1073

Cov.:

AF XY:

0.0845

AC XY:

6290

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.0455

Gnomad4 ASJ

AF:

0.0639

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0165

Gnomad4 NFE

AF:

0.0181

Gnomad4 OTH

AF:

0.0884

Alfa

AF:

0.0361

Hom.:

635

Bravo

AF:

0.0897

Asia WGS

AF:

0.183

AC:

635

AN:

3478

EpiCase

AF:

0.0183

EpiControl

AF:

0.0211

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Lys3569Lys in exon 73 of NEB: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 19.7% (795/4026) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs6717213). -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Mar 19, 2023	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Nemaline myopathy 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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