rs113445294

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007078.3(LDB3):c.690-4842G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 1,612,666 control chromosomes in the GnomAD database, including 1,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 517 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1397 hom. )

Consequence

LDB3
NM_007078.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.677

Publications

4 publications found

Variant links:

Genes affected

LDB3 (HGNC:15710): (LIM domain binding 3) This gene encodes a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. The protein encoded by this gene interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. Mutations in this gene have been associated with myofibrillar myopathy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been identified; all isoforms have N-terminal PDZ domains while only longer isoforms (1, 2 and 5) have C-terminal LIM domains. [provided by RefSeq, Jan 2010]

LDB3 Gene-Disease associations (from GenCC):

myofibrillar myopathy 4
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
familial dilated cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

LDB3 links:

ENSG00000289258 (HGNC:):

ENSG00000289258 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-86687054-G-A is Benign according to our data. Variant chr10-86687054-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3 link	c.690-4842G>A		intron_variant	Intron 5 of 13	ENST00000361373.9	NP_009009.1	O75112-1
LDB3	NM_001368067.1 link	c.345-15G>A		intron_variant	Intron 5 of 8	ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LDB3	ENST00000361373.9 link	c.690-4842G>A	intron_variant	Intron 5 of 13	1	NM_007078.3	ENSP00000355296.3	O75112-1
LDB3	ENST00000263066.11 link	c.345-15G>A	intron_variant	Intron 5 of 8	1	NM_001368067.1	ENSP00000263066.7	O75112-6
ENSG00000289258	ENST00000443292.2 link	c.2199-4842G>A	intron_variant	Intron 15 of 17	1		ENSP00000393132.2	C9JWU6

Frequencies

GnomAD3 genomes

AF:

0.0660

AC:

10023

AN:

151774

Hom.:

514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0407

Gnomad ASJ

AF:

0.0488

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0312

Gnomad FIN

AF:

0.0324

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0375

Gnomad OTH

AF:

0.0643

GnomAD2 exomes

AF:

0.0398

AC:

9911

AN:

248846

AF XY:

0.0385

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.0251

Gnomad ASJ exome

AF:

0.0533

Gnomad EAS exome

AF:

0.00284

Gnomad FIN exome

AF:

0.0312

Gnomad NFE exome

AF:

0.0360

Gnomad OTH exome

AF:

0.0440

GnomAD4 exome

AF:

0.0385

AC:

56205

AN:

1460776

Hom.:

1397

Cov.:

AF XY:

0.0383

AC XY:

27820

AN XY:

726658

show subpopulations

African (AFR)

AF:

0.153

AC:

5117

AN:

33450

American (AMR)

AF:

0.0256

AC:

1145

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0526

AC:

1375

AN:

26132

East Asian (EAS)

AF:

0.00149

AC:

AN:

39692

South Asian (SAS)

AF:

0.0355

AC:

3059

AN:

86228

European-Finnish (FIN)

AF:

0.0350

AC:

1866

AN:

53320

Middle Eastern (MID)

AF:

0.0862

AC:

486

AN:

5640

European-Non Finnish (NFE)

AF:

0.0362

AC:

40251

AN:

1111270

Other (OTH)

AF:

0.0472

AC:

2847

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2742

5485

8227

10970

13712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1552

3104

4656

6208

7760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0662

AC:

10052

AN:

151890

Hom.:

517

Cov.:

AF XY:

0.0631

AC XY:

4681

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.146

AC:

6035

AN:

41376

American (AMR)

AF:

0.0405

AC:

618

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0488

AC:

169

AN:

3466

East Asian (EAS)

AF:

0.00193

AC:

AN:

5170

South Asian (SAS)

AF:

0.0312

AC:

150

AN:

4802

European-Finnish (FIN)

AF:

0.0324

AC:

343

AN:

10576

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0375

AC:

2548

AN:

67936

Other (OTH)

AF:

0.0642

AC:

135

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0302

Hom.:

Bravo

AF:

0.0703

Asia WGS

AF:

0.0430

AC:

151

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

Sep 19, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Myofibrillar myopathy 4

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dilated cardiomyopathy 1C

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Myofibrillar Myopathy, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Left ventricular noncompaction cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.87

(source)

DANN

Benign

0.67

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over