rs397718862

chr2-151717388-A-AGGC

Variant summary

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

The NM_001164507.2(NEB):c.822+27_822+28insGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 1,422,986 control chromosomes in the GnomAD database, including 444,381 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (38670 hom., cov: 0)
  • Exomes 𝑓: 0.79 (405711 hom.)
• Consequence: NEB NM_001164507.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.499

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-151717388-A-AGGC is Benign according to our data. Variant chr2-151717388-A-AGGC is described in ClinVar as [Benign]. Clinvar id is 257832.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEB	NM_001164507.2	c.822+27_822+28insGCC		intron_variant		ENST00000427231.7
NEB	NM_001164508.2	c.822+27_822+28insGCC		intron_variant		ENST00000397345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEB	ENST00000397345.8	c.822+27_822+28insGCC		intron_variant		5	NM_001164508.2	P5
NEB	ENST00000427231.7	c.822+27_822+28insGCC		intron_variant		5	NM_001164507.2	A2
NEB	ENST00000409198.5	c.822+27_822+28insGCC		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103287 AN: 151722 Hom.: 38664 Cov.: 0

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.723

GnomAD3 exomes AF: 0.754 AC: 183267 AN: 243122 Hom.: 72025 AF XY: 0.756 AC XY: 99574 AN XY: 131766

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.862

Gnomad ASJ exome AF: 0.737

Gnomad EAS exome AF: 0.473

Gnomad SAS exome AF: 0.643

Gnomad FIN exome AF: 0.851

Gnomad NFE exome AF: 0.834

Gnomad OTH exome AF: 0.786

GnomAD4 exome AF: 0.790 AC: 1004056 AN: 1271144 Hom.: 405711 Cov.: 20 AF XY: 0.788 AC XY: 505748 AN XY: 641958

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.855

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.651

Gnomad4 FIN exome AF: 0.850

Gnomad4 NFE exome AF: 0.829

Gnomad4 OTH exome AF: 0.753

GnomAD4 genome AF: 0.680 AC: 103305 AN: 151842 Hom.: 38670 Cov.: 0 AF XY: 0.684 AC XY: 50735 AN XY: 74226

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.714

Alfa AF: 0.771 Hom.: 10404

Asia WGS AF: 0.497 AC: 1733 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

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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: rs397718862; hg19: chr2-152573902;