10-86699239-TTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTC

Variant names:

• chr10-86699239-TTCTC-T
• rs71019410
• NM_007078.3:c.896+6694_896+6697delCTCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_007078.3(LDB3):​c.896+6694_896+6697delCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,518,936 control chromosomes in the GnomAD database, including 1,315 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (960 hom., cov: 0)
  • Exomes 𝑓: 0.13 (355 hom.)
• Consequence: LDB3 NM_007078.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.30
• Publications: 5 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):

• 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

ENSG00000289258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 10-86699239-TTCTC-T is Benign according to our data. Variant chr10-86699239-TTCTC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007078.3. 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.896+6694_896+6697delCTCT		intron	N/A	NP_009009.1	O75112-1
	LDB3	NM_001368067.1	MANE Plus Clinical	c.756-13_756-10delCTCT		intron	N/A	NP_001354996.1	A0A0S2Z530
	LDB3	NM_001171610.2		c.1100+6694_1100+6697delCTCT		intron	N/A	NP_001165081.1	O75112-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB3	ENST00000361373.9	TSL:1 MANE Select	c.896+6669_896+6672delTCTC		intron	N/A	ENSP00000355296.3	O75112-1
	LDB3	ENST00000263066.11	TSL:1 MANE Plus Clinical	c.756-38_756-35delTCTC		intron	N/A	ENSP00000263066.7	O75112-6
	ENSG00000289258	ENST00000443292.2	TSL:1	c.2406-38_2406-35delTCTC		intron	N/A	ENSP00000393132.2	C9JWU6

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15228 AN: 148432 Hom.: 955 Cov.: 0

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0639

Gnomad ASJ AF: 0.0407

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0452

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0940

GnomAD2 exomes AF: 0.138 AC: 31104 AN: 225518 AF XY: 0.136

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.0560

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.128 AC: 175176 AN: 1370400 Hom.: 355 AF XY: 0.127 AC XY: 86666 AN XY: 684128

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.167 AC: 5354 AN: 32044

American (AMR) AF: 0.115 AC: 4974 AN: 43078

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2649 AN: 24800

East Asian (EAS) AF: 0.0355 AC: 1372 AN: 38638

South Asian (SAS) AF: 0.0797 AC: 6631 AN: 83156

European-Finnish (FIN) AF: 0.170 AC: 8584 AN: 50450

Middle Eastern (MID) AF: 0.0836 AC: 459 AN: 5490

European-Non Finnish (NFE) AF: 0.133 AC: 138026 AN: 1035830

Other (OTH) AF: 0.125 AC: 7127 AN: 56914

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.103 AC: 15254 AN: 148536 Hom.: 960 Cov.: 0 AF XY: 0.104 AC XY: 7485 AN XY: 72290

African (AFR) AF: 0.169 AC: 6849 AN: 40448

American (AMR) AF: 0.0638 AC: 950 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.0407 AC: 140 AN: 3440

East Asian (EAS) AF: 0.0248 AC: 124 AN: 5006

South Asian (SAS) AF: 0.0473 AC: 217 AN: 4592

European-Finnish (FIN) AF: 0.144 AC: 1447 AN: 10022

Middle Eastern (MID) AF: 0.0586 AC: 17 AN: 290

European-Non Finnish (NFE) AF: 0.0776 AC: 5192 AN: 66908

Other (OTH) AF: 0.0966 AC: 197 AN: 2040

Alfa AF: 0.0915 Hom.: 224

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
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: rs71019410; hg19: chr10-88458996;