Variant rs144077905 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.19732-39G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00939 in 1,483,466 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 92 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.315

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=-0.82).

BP6

Variant 2-151552815-C-G is Benign according to our data. Variant chr2-151552815-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 257782.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00677 (1030/152250) while in subpopulation NFE AF= 0.0105 (717/68026). AF 95% confidence interval is 0.0099. There are 6 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEB	NM_001164507.2 linkuse as main transcript	c.19732-39G>C		intron_variant		ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 linkuse as main transcript	c.19732-39G>C		intron_variant		ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEB	ENST00000397345.8 linkuse as main transcript	c.19732-39G>C		intron_variant		5	NM_001164508.2	ENSP00000380505	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.19732-39G>C		intron_variant		5	NM_001164507.2	ENSP00000416578	A2	P20929-3

Frequencies

GnomAD3 genomes

AF:

0.00677

AC:

1030

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00924

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00650

AC:

1338

AN:

205942

Hom.:

AF XY:

0.00676

AC XY:

745

AN XY:

110202

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00537

Gnomad ASJ exome

AF:

0.00722

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00461

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00659

GnomAD4 exome

AF:

0.00969

AC:

12900

AN:

1331216

Hom.:

Cov.:

AF XY:

0.00960

AC XY:

6384

AN XY:

665246

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00542

Gnomad4 ASJ exome

AF:

0.00640

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00509

Gnomad4 FIN exome

AF:

0.00218

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00819

GnomAD4 genome

AF:

0.00677

AC:

1030

AN:

152250

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

485

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00922

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00735

Hom.:

Bravo

AF:

0.00688

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely 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

-0.82

CADD

Benign

2.3

DANN

Benign

0.51

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

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