Variant rs62174683 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001164507.2(NEB):c.18580-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,608,658 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 26 hom., cov: 32)

Exomes 𝑓: 0.018 ( 288 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.773

Variant links:

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]

NEB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 2-151563751-G-A is Benign according to our data. Variant chr2-151563751-G-A is described in ClinVar as [Benign]. Clinvar id is 257774.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-151563751-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0149 (2269/152234) while in subpopulation NFE AF= 0.0227 (1547/68014). AF 95% confidence interval is 0.0218. There are 26 homozygotes in gnomad4. There are 1105 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEB	NM_001164507.2 linkuse as main transcript	c.18580-32C>T		intron_variant		ENST00000427231.7
NEB	NM_001164508.2 linkuse as main transcript	c.18580-32C>T		intron_variant		ENST00000397345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEB	ENST00000397345.8 linkuse as main transcript	c.18580-32C>T		intron_variant		5	NM_001164508.2	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.18580-32C>T		intron_variant		5	NM_001164507.2	A2	P20929-3

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2268

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00348

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0150

AC:

3737

AN:

248926

Hom.:

AF XY:

0.0151

AC XY:

2043

AN XY:

135030

show subpopulations

Gnomad AFR exome

AF:

0.00297

Gnomad AMR exome

AF:

0.00682

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00480

Gnomad FIN exome

AF:

0.0245

Gnomad NFE exome

AF:

0.0216

Gnomad OTH exome

AF:

0.0164

GnomAD4 exome

AF:

0.0183

AC:

26720

AN:

1456424

Hom.:

288

Cov.:

AF XY:

0.0183

AC XY:

13239

AN XY:

724928

show subpopulations

Gnomad4 AFR exome

AF:

0.00237

Gnomad4 AMR exome

AF:

0.00667

Gnomad4 ASJ exome

AF:

0.0220

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00455

Gnomad4 FIN exome

AF:

0.0233

Gnomad4 NFE exome

AF:

0.0208

Gnomad4 OTH exome

AF:

0.0175

GnomAD4 genome

AF:

0.0149

AC:

2269

AN:

152234

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1105

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00347

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0283

Gnomad4 NFE

AF:

0.0227

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.70

CADD

Benign

0.36

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over