Genetic Variant LDB3:c.896+6686_896+6697delCTCTCTCTCTCT (chr10-86699239-TTCTCTCTCTCTC-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_007078.3(LDB3):c.896+6686_896+6697delCTCTCTCTCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,562,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

LDB3
NM_007078.3 intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.30

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:

ENSG00000289258 (HGNC:):

ENSG00000289258 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 10-86699239-TTCTCTCTCTCTC-T is Benign according to our data. Variant chr10-86699239-TTCTCTCTCTCTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041152.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000074 (11/148744) while in subpopulation NFE AF= 0.000149 (10/67010). AF 95% confidence interval is 0.0000802. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3 link	c.896+6686_896+6697delCTCTCTCTCTCT		intron_variant	Intron 7 of 13	ENST00000361373.9	NP_009009.1	O75112-1
LDB3	NM_001368067.1 link	c.756-21_756-10delCTCTCTCTCTCT		intron_variant	Intron 8 of 8	ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LDB3	ENST00000361373.9 link	c.896+6669_896+6680delTCTCTCTCTCTC	intron_variant	Intron 7 of 13	1	NM_007078.3	ENSP00000355296.3	O75112-1
LDB3	ENST00000263066.11 link	c.756-38_756-27delTCTCTCTCTCTC	intron_variant	Intron 8 of 8	1	NM_001368067.1	ENSP00000263066.7	O75112-6
ENSG00000289258	ENST00000443292.2 link	c.2406-38_2406-27delTCTCTCTCTCTC	intron_variant	Intron 17 of 17	1		ENSP00000393132.2	C9JWU6

Frequencies

GnomAD3 genomes

AF:

0.0000740

AC:

AN:

148744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000989

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

166

AN:

1414032

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

705828

show subpopulations

Gnomad4 AFR exome

AF:

0.0000618

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000514

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.0000385

Gnomad4 NFE exome

AF:

0.000143

Gnomad4 OTH exome

AF:

0.0000512

GnomAD4 genome

AF:

0.0000740

AC:

AN:

148744

Hom.:

Cov.:

AF XY:

0.0000553

AC XY:

AN XY:

72356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000989

Gnomad4 NFE

AF:

0.000149

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LDB3-related disorder

Benign:1

Sep 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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