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. The variant received -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
• Publications: 4 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443292.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB3	NM_001368064.1		c.-23-350A>T		intron	N/A	NP_001354993.1	V5T7C5
	LDB3	NM_001368063.1		c.-23-350A>T		intron	N/A	NP_001354992.1	A0A0S2Z501
	LDB3	NM_001368068.1		c.-23-350A>T		intron	N/A	NP_001354997.1	A0A0S2Z530

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289258	ENST00000443292.2	TSL:1	c.1487-350A>T		intron	N/A	ENSP00000393132.2	C9JWU6
	LDB3	ENST00000945670.1		c.-25A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000615729.1
	LDB3	ENST00000945671.1		c.-97A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000615730.1

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

African (AFR) AF: 0.909 AC: 5442 AN: 5990

American (AMR) AF: 0.771 AC: 8662 AN: 11238

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 3616 AN: 4892

East Asian (EAS) AF: 0.803 AC: 7821 AN: 9744

South Asian (SAS) AF: 0.793 AC: 27237 AN: 34342

European-Finnish (FIN) AF: 0.728 AC: 6501 AN: 8936

Middle Eastern (MID) AF: 0.765 AC: 545 AN: 712

European-Non Finnish (NFE) AF: 0.699 AC: 78705 AN: 112554

Other (OTH) AF: 0.734 AC: 7597 AN: 10344

GnomAD4 genome AF: 0.778 AC: 118276 AN: 152070 Hom.: 46650 Cov.: 32 AF XY: 0.782 AC XY: 58099 AN XY: 74318

African (AFR) AF: 0.912 AC: 37872 AN: 41516

American (AMR) AF: 0.769 AC: 11753 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2610 AN: 3472

East Asian (EAS) AF: 0.802 AC: 4103 AN: 5114

South Asian (SAS) AF: 0.804 AC: 3870 AN: 4816

European-Finnish (FIN) AF: 0.731 AC: 7741 AN: 10586

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47733 AN: 67954

Other (OTH) AF: 0.754 AC: 1595 AN: 2114

Alfa AF: 0.686 Hom.: 2290

Bravo AF: 0.783

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		-0.69
PromoterAI		-0.27	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2675692; hg19: chr10-88428076;