NM_007078.3:c.689+3825G>C

Variant names:

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.689+3825G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,606,888 control chromosomes in the GnomAD database, including 419,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34777 hom., cov: 32)

Exomes 𝑓: 0.72 ( 385008 hom. )

Consequence

LDB3
NM_007078.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:3

Conservation

PhyloP100: -0.492

Publications

10 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=-0.92).

BP6

Variant 10-86685628-G-C is Benign according to our data. Variant chr10-86685628-G-C is described in ClinVar as Benign. ClinVar VariationId is 257337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3 link	c.689+3825G>C		intron_variant	Intron 5 of 13	ENST00000361373.9	NP_009009.1	O75112-1
LDB3	NM_001368067.1 link	c.322-50G>C		intron_variant	Intron 4 of 8	ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LDB3	ENST00000361373.9 link	c.689+3825G>C	intron_variant	Intron 5 of 13	1	NM_007078.3	ENSP00000355296.3	O75112-1
LDB3	ENST00000263066.11 link	c.322-50G>C	intron_variant	Intron 4 of 8	1	NM_001368067.1	ENSP00000263066.7	O75112-6
ENSG00000289258	ENST00000443292.2 link	c.2198+3825G>C	intron_variant	Intron 15 of 17	1		ENSP00000393132.2	C9JWU6

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101848

AN:

151916

Hom.:

34770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.787

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.747

Gnomad OTH

AF:

0.679

GnomAD2 exomes

AF:

0.675

AC:

168369

AN:

249358

AF XY:

0.692

show subpopulations

Gnomad AFR exome

AF:

0.592

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.747

Gnomad EAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.647

Gnomad NFE exome

AF:

0.744

Gnomad OTH exome

AF:

0.695

GnomAD4 exome

AF:

0.724

AC:

1052756

AN:

1454854

Hom.:

385008

Cov.:

AF XY:

0.727

AC XY:

526907

AN XY:

724346

show subpopulations

African (AFR)

AF:

0.587

AC:

19553

AN:

33316

American (AMR)

AF:

0.496

AC:

22193

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

19473

AN:

26096

East Asian (EAS)

AF:

0.462

AC:

18297

AN:

39646

South Asian (SAS)

AF:

0.793

AC:

68294

AN:

86124

European-Finnish (FIN)

AF:

0.656

AC:

34887

AN:

53204

Middle Eastern (MID)

AF:

0.767

AC:

4414

AN:

5758

European-Non Finnish (NFE)

AF:

0.744

AC:

822978

AN:

1105850

Other (OTH)

AF:

0.709

AC:

42667

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

14448

28896

43343

57791

72239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19938

39876

59814

79752

99690

<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:

0.670

AC:

101887

AN:

152034

Hom.:

34777

Cov.:

AF XY:

0.665

AC XY:

49389

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.588

AC:

24356

AN:

41434

American (AMR)

AF:

0.575

AC:

8794

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.749

AC:

2596

AN:

3468

East Asian (EAS)

AF:

0.470

AC:

2425

AN:

5156

South Asian (SAS)

AF:

0.788

AC:

3800

AN:

4820

European-Finnish (FIN)

AF:

0.641

AC:

6783

AN:

10576

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.747

AC:

50811

AN:

67988

Other (OTH)

AF:

0.673

AC:

1418

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1681

3362

5042

6723

8404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.719

Hom.:

7283

Bravo

AF:

0.655

Asia WGS

AF:

0.617

AC:

2145

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dilated cardiomyopathy 1C

Uncertain:1

Sep 11, 2014

Cytogenetics- Mohapatra Lab, Banaras Hindu University

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:case-control

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: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

-0.92

CADD

Benign

2.1

(source)

DANN

Benign

0.55

PhyloP100

-0.49

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