Variant 10-86668319-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001368064.1(LDB3):c.-23-350A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 350,822 control chromosomes in the GnomAD database, including 100,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.78 ( 46650 hom., cov: 32)

Exomes 𝑓: 0.74 ( 54230 hom. )

Consequence

LDB3
NM_001368064.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.687

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-86668319-A-T is Benign according to our data. Variant chr10-86668319-A-T is described in ClinVar as [Benign]. Clinvar id is 683005.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect
LDB3	NM_001368063.1 linkuse as main transcript	c.-23-350A>T	intron_variant
LDB3	NM_001368064.1 linkuse as main transcript	c.-23-350A>T	intron_variant
LDB3	NM_001368068.1 linkuse as main transcript	c.-23-350A>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Appris
LDB3	ENST00000688001.1 linkuse as main transcript	c.-23-350A>T	intron_variant	A2
LDB3	ENST00000688785.1 linkuse as main transcript	c.-23-350A>T	intron_variant
LDB3	ENST00000691462.1 linkuse as main transcript	c.-23-350A>T	intron_variant
LDB3	ENST00000687856.1 linkuse as main transcript	c.-23-350A>T	intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.778

AC:

118153

AN:

151950

Hom.:

46587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.912

Gnomad AMI

AF:

0.849

Gnomad AMR

AF:

0.768

Gnomad ASJ

AF:

0.752

Gnomad EAS

AF:

0.802

Gnomad SAS

AF:

0.804

Gnomad FIN

AF:

0.731

Gnomad MID

AF:

0.771

Gnomad NFE

AF:

0.702

Gnomad OTH

AF:

0.753

GnomAD4 exome

AF:

0.735

AC:

146126

AN:

198752

Hom.:

54230

AF XY:

0.740

AC XY:

79021

AN XY:

106776

show subpopulations

Gnomad4 AFR exome

AF:

0.909

Gnomad4 AMR exome

AF:

0.771

Gnomad4 ASJ exome

AF:

0.739

Gnomad4 EAS exome

AF:

0.803

Gnomad4 SAS exome

AF:

0.793

Gnomad4 FIN exome

AF:

0.728

Gnomad4 NFE exome

AF:

0.699

Gnomad4 OTH exome

AF:

0.734

GnomAD4 genome

AF:

0.778

AC:

118276

AN:

152070

Hom.:

46650

Cov.:

AF XY:

0.782

AC XY:

58099

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.912

Gnomad4 AMR

AF:

0.769

Gnomad4 ASJ

AF:

0.752

Gnomad4 EAS

AF:

0.802

Gnomad4 SAS

AF:

0.804

Gnomad4 FIN

AF:

0.731

Gnomad4 NFE

AF:

0.702

Gnomad4 OTH

AF:

0.754

Alfa

AF:

0.686

Hom.:

2290

Bravo

AF:

0.783

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.1

DANN

Benign

0.58

Splicing

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