ENST00000443292.2:c.1487-350A>T

Variant names:

• chr10-86668319-A-T
• rs2675692
• ENST00000443292.2:c.1487-350A>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000443292.2(ENSG00000289258):​c.1487-350A>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: ENSG00000289258 ENST00000443292.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.687

Genes affected

ENSG00000289258 (HGNC:):

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]

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3	c.-275A>T		upstream_gene_variant		ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.-275A>T		upstream_gene_variant		ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289258	ENST00000443292.2	c.1487-350A>T		intron_variant	Intron 11 of 17	1		ENSP00000393132.2
LDB3	ENST00000361373.9	c.-275A>T		upstream_gene_variant		1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.-275A>T		upstream_gene_variant		1	NM_001368067.1	ENSP00000263066.7

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118153 AN: 151950 Hom.: 46587 Cov.: 32

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

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.: 32 AF XY: 0.782 AC XY: 58099 AN XY: 74318

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

Submissions by phenotype

not provided Benign:1

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. -

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

Other links and lift over

dbSNP: rs2675692; hg19: chr10-88428076;