10-86668545-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_007078.3(LDB3):c.-49C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 733,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

LDB3
NM_007078.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.220

Publications

0 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-86668545-C-T is Benign according to our data. Variant chr10-86668545-C-T is described in ClinVar as Benign. ClinVar VariationId is 378078.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000269 (41/152318) while in subpopulation AFR AF = 0.00089 (37/41582). AF 95% confidence interval is 0.000663. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 34. 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.-49C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_009009.1	O75112-1
LDB3	NM_001368067.1	MANE Plus Clinical	c.-49C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001354996.1	A0A0S2Z530
LDB3	NM_007078.3	MANE Select	c.-49C>T	5_prime_UTR	Exon 1 of 14	NP_009009.1	O75112-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LDB3	ENST00000361373.9	TSL:1 MANE Select	c.-49C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000355296.3	O75112-1
LDB3	ENST00000263066.11	TSL:1 MANE Plus Clinical	c.-49C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000263066.7	O75112-6
LDB3	ENST00000361373.9	TSL:1 MANE Select	c.-49C>T	5_prime_UTR	Exon 1 of 14	ENSP00000355296.3	O75112-1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000620

AC:

AN:

581080

Hom.:

Cov.:

AF XY:

0.0000604

AC XY:

AN XY:

314648

show subpopulations

African (AFR)

AF:

0.000603

AC:

AN:

16584

American (AMR)

AF:

0.0000549

AC:

AN:

36438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20228

East Asian (EAS)

AF:

0.0000302

AC:

AN:

33128

South Asian (SAS)

AF:

0.00

AC:

AN:

64710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38414

Middle Eastern (MID)

AF:

0.000489

AC:

AN:

4088

European-Non Finnish (NFE)

AF:

0.0000476

AC:

AN:

335882

Other (OTH)

AF:

0.000158

AC:

AN:

31608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000269

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41582

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000142

Hom.:

Bravo

AF:

0.000249

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

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

-0.22

PromoterAI

-0.066

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over