rs142314464

Variant names:

• chr2-151512883-C-CAACA
• rs142314464
• NM_001164507.2:c.23242-50_23242-47dupTGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000397345.8(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 ENST00000397345.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.328
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397345.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEB	NM_001164507.2	MANE Plus Clinical	c.23242-50_23242-47dupTGTT		intron	N/A	NP_001157979.2
	NEB	NM_001164508.2	MANE Select	c.23242-50_23242-47dupTGTT		intron	N/A	NP_001157980.2
	NEB	NM_001271208.2		c.23347-50_23347-47dupTGTT		intron	N/A	NP_001258137.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEB	ENST00000397345.8	TSL:5 MANE Select	c.23242-47_23242-46insTGTT		intron	N/A	ENSP00000380505.3
	NEB	ENST00000427231.7	TSL:5 MANE Plus Clinical	c.23242-47_23242-46insTGTT		intron	N/A	ENSP00000416578.2
	NEB	ENST00000409198.5	TSL:5	c.18139-47_18139-46insTGTT		intron	N/A	ENSP00000386259.1

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

GnomAD2 exomes AF: 0.0192 AC: 3740 AN: 195180 AF XY: 0.0183

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 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

African (AFR) AF: 0.0523 AC: 1460 AN: 27922

American (AMR) AF: 0.0106 AC: 407 AN: 38490

Ashkenazi Jewish (ASJ) AF: 0.0229 AC: 547 AN: 23904

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37466

South Asian (SAS) AF: 0.00700 AC: 536 AN: 76560

European-Finnish (FIN) AF: 0.0346 AC: 1772 AN: 51198

Middle Eastern (MID) AF: 0.00971 AC: 51 AN: 5252

European-Non Finnish (NFE) AF: 0.0198 AC: 17148 AN: 864668

Other (OTH) AF: 0.0199 AC: 1013 AN: 50924

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

African (AFR) AF: 0.0533 AC: 2216 AN: 41560

American (AMR) AF: 0.0133 AC: 204 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4830

European-Finnish (FIN) AF: 0.0406 AC: 430 AN: 10596

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0197 AC: 1337 AN: 68008

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0254 Hom.: 13

Bravo AF: 0.0285

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs142314464; hg19: chr2-152369397;