10-86699239-TTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS1

The NM_007078.3(LDB3):c.896+6696_896+6697dupCT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0033 ( 0 hom. )

Consequence

LDB3
NM_007078.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0920

Publications

5 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):

dilated cardiomyopathy
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: ClinGen
myofibrillar myopathy 4
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 10-86699239-T-TTC is Benign according to our data. Variant chr10-86699239-T-TTC is described in ClinVar as Benign. ClinVar VariationId is 163842.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00315 (469/148846) while in subpopulation SAS AF = 0.00958 (44/4592). AF 95% confidence interval is 0.00734. There are 1 homozygotes in GnomAd4. There are 220 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LDB3	NM_007078.3	MANE Select	c.896+6696_896+6697dupCT	intron	N/A	NP_009009.1	O75112-1
LDB3	NM_001368067.1	MANE Plus Clinical	c.756-11_756-10dupCT	intron	N/A	NP_001354996.1	A0A0S2Z530
LDB3	NM_001171610.2		c.1100+6696_1100+6697dupCT	intron	N/A	NP_001165081.1	O75112-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LDB3	ENST00000361373.9	TSL:1 MANE Select	c.896+6668_896+6669insTC	intron	N/A	ENSP00000355296.3	O75112-1
LDB3	ENST00000263066.11	TSL:1 MANE Plus Clinical	c.756-39_756-38insTC	intron	N/A	ENSP00000263066.7	O75112-6
ENSG00000289258	ENST00000443292.2	TSL:1	c.2406-39_2406-38insTC	intron	N/A	ENSP00000393132.2	C9JWU6

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

463

AN:

148738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00144

Gnomad AMI

AF:

0.00112

Gnomad AMR

AF:

0.00248

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00737

Gnomad SAS

AF:

0.00957

Gnomad FIN

AF:

0.000791

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.00385

Gnomad OTH

AF:

0.00640

GnomAD2 exomes

AF:

0.00342

AC:

771

AN:

225518

AF XY:

0.00374

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.000535

Gnomad EAS exome

AF:

0.00675

Gnomad FIN exome

AF:

0.000578

Gnomad NFE exome

AF:

0.00315

Gnomad OTH exome

AF:

0.00251

GnomAD4 exome

AF:

0.00330

AC:

4659

AN:

1412776

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2357

AN XY:

705212

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000833

AC:

AN:

32408

American (AMR)

AF:

0.00176

AC:

AN:

44366

Ashkenazi Jewish (ASJ)

AF:

0.00105

AC:

AN:

25644

East Asian (EAS)

AF:

0.00798

AC:

311

AN:

38964

South Asian (SAS)

AF:

0.00681

AC:

578

AN:

84910

European-Finnish (FIN)

AF:

0.000809

AC:

AN:

51934

Middle Eastern (MID)

AF:

0.00530

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.00315

AC:

3375

AN:

1070304

Other (OTH)

AF:

0.00326

AC:

191

AN:

58590

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.330

Heterozygous variant carriers

284

568

853

1137

1421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

142

284

426

568

710

<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:

0.00315

AC:

469

AN:

148846

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

220

AN XY:

72470

show subpopulations

African (AFR)

AF:

0.00158

AC:

AN:

40496

American (AMR)

AF:

0.00247

AC:

AN:

14960

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3442

East Asian (EAS)

AF:

0.00739

AC:

AN:

5008

South Asian (SAS)

AF:

0.00958

AC:

AN:

4592

European-Finnish (FIN)

AF:

0.000791

AC:

AN:

10114

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00385

AC:

258

AN:

67000

Other (OTH)

AF:

0.00634

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00306

Hom.:

224

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.092

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over