rs16830128

chr2-151513538-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001164507.2(NEB):c.23241+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,424,300 control chromosomes in the GnomAD database, including 766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (79 hom., cov: 32)
  • Exomes 𝑓: 0.011 (687 hom.)
• Consequence: NEB NM_001164507.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-151513538-A-G is Benign according to our data. Variant chr2-151513538-A-G is described in ClinVar as [Benign]. Clinvar id is 257798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEB	NM_001164507.2	c.23241+42T>C		intron_variant		ENST00000427231.7
NEB	NM_001164508.2	c.23241+42T>C		intron_variant		ENST00000397345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEB	ENST00000397345.8	c.23241+42T>C		intron_variant		5	NM_001164508.2	P5
NEB	ENST00000427231.7	c.23241+42T>C		intron_variant		5	NM_001164507.2	A2

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2227 AN: 152170 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0755

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00195

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.0233 AC: 4180 AN: 179392 Hom.: 206 AF XY: 0.0259 AC XY: 2456 AN XY: 94820

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.00270

Gnomad ASJ exome AF: 0.0315

Gnomad EAS exome AF: 0.140

Gnomad SAS exome AF: 0.0675

Gnomad FIN exome AF: 0.0000559

Gnomad NFE exome AF: 0.00198

Gnomad OTH exome AF: 0.0149

GnomAD4 exome AF: 0.0111 AC: 14144 AN: 1272012 Hom.: 687 Cov.: 17 AF XY: 0.0129 AC XY: 8209 AN XY: 635660

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.00289

Gnomad4 ASJ exome AF: 0.0311

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.0679

Gnomad4 FIN exome AF: 0.000277

Gnomad4 NFE exome AF: 0.00147

Gnomad4 OTH exome AF: 0.0191

GnomAD4 genome AF: 0.0148 AC: 2261 AN: 152288 Hom.: 79 Cov.: 32 AF XY: 0.0162 AC XY: 1204 AN XY: 74472

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0764

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.00907 Hom.: 10

Bravo AF: 0.0140

Asia WGS AF: 0.124 AC: 428 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.8
Dann	Benign	0.63

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: rs16830128; hg19: chr2-152370052; COSMIC: COSV51419678; COSMIC: COSV51419678;