rs113445294

Variant names:

• chr10-86687054-G-A
• rs113445294
• NM_007078.3:c.690-4842G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-86687054-G-A
• chr10-86687054-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001171610.2(LDB3):​c.690-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 1,612,666 control chromosomes in the GnomAD database, including 1,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (517 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1397 hom.)
• Consequence: LDB3 NM_001171610.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.677
• Publications: 4 publications found

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):

• myofibrillar myopathy 4

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• familial dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000289258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-86687054-G-A is Benign according to our data. Variant chr10-86687054-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171610.2. 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_007078.3	MANE Select	c.690-4842G>A		intron	N/A	NP_009009.1
	LDB3	NM_001368067.1	MANE Plus Clinical	c.345-15G>A		intron	N/A	NP_001354996.1
	LDB3	NM_001171610.2		c.690-15G>A		intron	N/A	NP_001165081.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB3	ENST00000361373.9	TSL:1 MANE Select	c.690-4842G>A		intron	N/A	ENSP00000355296.3
	LDB3	ENST00000263066.11	TSL:1 MANE Plus Clinical	c.345-15G>A		intron	N/A	ENSP00000263066.7
	ENSG00000289258	ENST00000443292.2	TSL:1	c.2199-4842G>A		intron	N/A	ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10023 AN: 151774 Hom.: 514 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0488

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0312

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0643

GnomAD2 exomes AF: 0.0398 AC: 9911 AN: 248846 AF XY: 0.0385

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.0251

Gnomad ASJ exome AF: 0.0533

Gnomad EAS exome AF: 0.00284

Gnomad FIN exome AF: 0.0312

Gnomad NFE exome AF: 0.0360

Gnomad OTH exome AF: 0.0440

GnomAD4 exome AF: 0.0385 AC: 56205 AN: 1460776 Hom.: 1397 Cov.: 32 AF XY: 0.0383 AC XY: 27820 AN XY: 726658

African (AFR) AF: 0.153 AC: 5117 AN: 33450

American (AMR) AF: 0.0256 AC: 1145 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0526 AC: 1375 AN: 26132

East Asian (EAS) AF: 0.00149 AC: 59 AN: 39692

South Asian (SAS) AF: 0.0355 AC: 3059 AN: 86228

European-Finnish (FIN) AF: 0.0350 AC: 1866 AN: 53320

Middle Eastern (MID) AF: 0.0862 AC: 486 AN: 5640

European-Non Finnish (NFE) AF: 0.0362 AC: 40251 AN: 1111270

Other (OTH) AF: 0.0472 AC: 2847 AN: 60328

GnomAD4 genome AF: 0.0662 AC: 10052 AN: 151890 Hom.: 517 Cov.: 32 AF XY: 0.0631 AC XY: 4681 AN XY: 74214

African (AFR) AF: 0.146 AC: 6035 AN: 41376

American (AMR) AF: 0.0405 AC: 618 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0488 AC: 169 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5170

South Asian (SAS) AF: 0.0312 AC: 150 AN: 4802

European-Finnish (FIN) AF: 0.0324 AC: 343 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0375 AC: 2548 AN: 67936

Other (OTH) AF: 0.0642 AC: 135 AN: 2104

Alfa AF: 0.0302 Hom.: 27

Bravo AF: 0.0703

Asia WGS AF: 0.0430 AC: 151 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	not specified (3)
-	-	2	Myofibrillar myopathy 4 (2)
-	-	1	Dilated cardiomyopathy 1C (1)
-	-	1	Left ventricular noncompaction cardiomyopathy (1)
-	-	1	Myofibrillar Myopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.67
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs113445294; hg19: chr10-88446811;