rs142314464

chr2-151512883-C-CAACA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001164507.2(NEB):c.23242-47_23242-46insTGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,328,656 control chromosomes in the GnomAD database, including 421 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (86 hom., cov: 32)
  • Exomes 𝑓: 0.019 (335 hom.)
• Consequence: NEB NM_001164507.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.328

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 -10 ACMG points.

• BP6: Variant 2-151512883-C-CAACA is Benign according to our data. Variant chr2-151512883-C-CAACA is described in ClinVar as [Benign]. Clinvar id is 257799.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEB	NM_001164507.2	c.23242-47_23242-46insTGTT		intron_variant		ENST00000427231.7
NEB	NM_001164508.2	c.23242-47_23242-46insTGTT		intron_variant		ENST00000397345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEB	ENST00000397345.8	c.23242-47_23242-46insTGTT		intron_variant		5	NM_001164508.2	P5
NEB	ENST00000427231.7	c.23242-47_23242-46insTGTT		intron_variant		5	NM_001164507.2	A2

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4358 AN: 152154 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0273

GnomAD3 exomes AF: 0.0192 AC: 3740 AN: 195180 Hom.: 51 AF XY: 0.0183 AC XY: 1904 AN XY: 104156

Gnomad AFR exome AF: 0.0492

Gnomad AMR exome AF: 0.00947

Gnomad ASJ exome AF: 0.0223

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00631

Gnomad FIN exome AF: 0.0357

Gnomad NFE exome AF: 0.0210

Gnomad OTH exome AF: 0.0221

GnomAD4 exome AF: 0.0195 AC: 22935 AN: 1176384 Hom.: 335 Cov.: 15 AF XY: 0.0189 AC XY: 11202 AN XY: 594166

Gnomad4 AFR exome AF: 0.0523

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0229

Gnomad4 EAS exome AF: 0.0000267

Gnomad4 SAS exome AF: 0.00700

Gnomad4 FIN exome AF: 0.0346

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0287 AC: 4376 AN: 152272 Hom.: 86 Cov.: 32 AF XY: 0.0293 AC XY: 2178 AN XY: 74450

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0254 Hom.: 13

Bravo AF: 0.0285

Asia WGS AF: 0.00751 AC: 26 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

Mar 07, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142314464; hg19: chr2-152369397;