rs149510427

Variant names:

• chr2-151531078-G-A
• rs149510427
• NM_001164507.2:c.21546C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-151531078-G-A
• chr2-151531078-G-C
• chr2-151531078-G-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001164508.2(NEB):​c.21546C>T​(p.Asn7182Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00651 in 1,611,652 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (276 hom.)
• Consequence: NEB NM_001164508.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 6.51

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]

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 2-151531078-G-A is Benign according to our data. Variant chr2-151531078-G-A is described in ClinVar as [Benign]. Clinvar id is 95113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEB	NM_001164507.2	c.21546C>T	p.Asn7182Asn	synonymous_variant	Exon 145 of 182	ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2	c.21546C>T	p.Asn7182Asn	synonymous_variant	Exon 145 of 182	ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEB	ENST00000397345.8	c.21546C>T	p.Asn7182Asn	synonymous_variant	Exon 145 of 182	5	NM_001164508.2	ENSP00000380505.3
NEB	ENST00000427231.7	c.21546C>T	p.Asn7182Asn	synonymous_variant	Exon 145 of 182	5	NM_001164507.2	ENSP00000416578.2

Frequencies

GnomAD3 genomes AF: 0.00782 AC: 1190 AN: 152078 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.0160 AC: 3950 AN: 247620 Hom.: 99 AF XY: 0.0136 AC XY: 1831 AN XY: 134256

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.0605

Gnomad ASJ exome AF: 0.0145

Gnomad EAS exome AF: 0.0630

Gnomad SAS exome AF: 0.00291

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.00637 AC: 9293 AN: 1459456 Hom.: 276 Cov.: 31 AF XY: 0.00610 AC XY: 4428 AN XY: 726044

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.0578

Gnomad4 ASJ exome AF: 0.0143

Gnomad4 EAS exome AF: 0.0898

Gnomad4 SAS exome AF: 0.00308

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.00720

GnomAD4 genome AF: 0.00785 AC: 1194 AN: 152196 Hom.: 30 Cov.: 32 AF XY: 0.00895 AC XY: 666 AN XY: 74412

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.0708

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00282 Hom.: 1

Bravo AF: 0.0103

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 18, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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. -

Sep 27, 2016

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 24, 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. -

Nemaline myopathy 2 Benign:3

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 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. -

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	-0.32
CADD	Benign	7.4
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs149510427; hg19: chr2-152387592; COSMIC: COSV51420235; COSMIC: COSV51420235;