rs13031275

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001164508.2(NEB):c.25395T>G(p.Ser8465Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 1,590,030 control chromosomes in the GnomAD database, including 2,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 154 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2618 hom. )

Consequence

NEB
NM_001164508.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.804

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:23207): (replication timing regulatory factor 1) This gene encodes a protein that shares homology with the yeast teleomere binding protein, Rap1 interacting factor 1. This protein localizes to aberrant telomeres may be involved in DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

RIF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-151489980-A-C is Benign according to our data. Variant chr2-151489980-A-C is described in ClinVar as [Benign]. Clinvar id is 129735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151489980-A-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.804 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2 link	c.25395T>G	p.Ser8465Ser	synonymous_variant	Exon 181 of 182	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 link	c.25395T>G	p.Ser8465Ser	synonymous_variant	Exon 181 of 182	ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEB	ENST00000397345.8 link	c.25395T>G	p.Ser8465Ser	synonymous_variant	Exon 181 of 182	5	NM_001164508.2	ENSP00000380505.3		P20929-2
NEB	ENST00000427231.7 link	c.25395T>G	p.Ser8465Ser	synonymous_variant	Exon 181 of 182	5	NM_001164507.2	ENSP00000416578.2		P20929-3

Frequencies

GnomAD3 genomes

AF:

0.0379

AC:

5775

AN:

152176

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.0287

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0607

Gnomad OTH

AF:

0.0373

GnomAD3 exomes

AF:

0.0418

AC:

10392

AN:

248880

Hom.:

298

AF XY:

0.0425

AC XY:

5741

AN XY:

134998

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0451

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0217

Gnomad FIN exome

AF:

0.0311

Gnomad NFE exome

AF:

0.0657

Gnomad OTH exome

AF:

0.0437

GnomAD4 exome

AF:

0.0561

AC:

80722

AN:

1437736

Hom.:

2618

Cov.:

AF XY:

0.0554

AC XY:

39726

AN XY:

716786

show subpopulations

Gnomad4 AFR exome

AF:

0.00966

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.0458

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0336

Gnomad4 NFE exome

AF:

0.0657

Gnomad4 OTH exome

AF:

0.0456

GnomAD4 genome

AF:

0.0379

AC:

5772

AN:

152294

Hom.:

154

Cov.:

AF XY:

0.0352

AC XY:

2621

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.0267

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0287

Gnomad4 NFE

AF:

0.0607

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0581

Hom.:

478

Bravo

AF:

0.0375

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.0599

EpiControl

AF:

0.0622

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 26, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Nov 26, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Ser8500Ser in exon 182 of NEB: This variant is not expected to have clinical s ignificance because it has been identified in 6.5% (530/8194) of European Americ an chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS/; dbSNP rs13031275). -

Nemaline myopathy 2

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.9

DANN

Benign

0.75

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