chr2-151525940-C-G

Position:

chr2-151525940-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001164507.2(NEB):c.22161+18G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,588,490 control chromosomes in the GnomAD database, including 300,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27116 hom., cov: 33)

Exomes 𝑓: 0.61 ( 273212 hom. )

Consequence

NEB
NM_001164507.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.69

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:

RIF1 (HGNC:):

RIF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-151525940-C-G is Benign according to our data. Variant chr2-151525940-C-G is described in ClinVar as [Benign]. Clinvar id is 95116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-151525940-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEB	NM_001164507.2 linkuse as main transcript	c.22161+18G>C		intron_variant		ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2 linkuse as main transcript	c.22161+18G>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.22161+18G>C		intron_variant		5	NM_001164508.2	ENSP00000380505	P5	P20929-2
NEB	ENST00000427231.7 linkuse as main transcript	c.22161+18G>C		intron_variant		5	NM_001164507.2	ENSP00000416578	A2	P20929-3

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90096

AN:

152010

Hom.:

27090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.697

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.588

GnomAD3 exomes

AF:

0.603

AC:

150066

AN:

248986

Hom.:

46259

AF XY:

0.592

AC XY:

79907

AN XY:

135054

show subpopulations

Gnomad AFR exome

AF:

0.516

Gnomad AMR exome

AF:

0.732

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.590

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.619

GnomAD4 exome

AF:

0.614

AC:

881395

AN:

1436360

Hom.:

273212

Cov.:

AF XY:

0.608

AC XY:

435211

AN XY:

716194

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.521

Gnomad4 EAS exome

AF:

0.634

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.641

Gnomad4 NFE exome

AF:

0.627

Gnomad4 OTH exome

AF:

0.603

GnomAD4 genome

AF:

0.593

AC:

90165

AN:

152130

Hom.:

27116

Cov.:

AF XY:

0.594

AC XY:

44183

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.697

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.592

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.644

Gnomad4 NFE

AF:

0.626

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.549

Hom.:

2977

Bravo

AF:

0.598

Asia WGS

AF:

0.490

AC:

1707

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 27, 2017	Variant summary: The NEB c.22266+18G>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 71749/120734 control chromosomes (21816 homozygotes) at a frequency of 0.5942734, which is approximately 168 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), evidence that this variant is a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 05, 2013	- -

Nemaline myopathy 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Arthrogryposis multiplex congenita 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.52

DANN

Benign

0.27

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