NM_007078.3:c.896+6686_896+6697delCTCTCTCTCTCT

Variant names:

• chr10-86699239-TTCTCTCTCTCTC-T
• rs71019410
• NM_007078.3:c.896+6686_896+6697delCTCTCTCTCTCT

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS1

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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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: Likely_benign. The variant received -5 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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+6686_896+6697delCTCTCTCTCTCT		intron	N/A	NP_009009.1	O75112-1
	LDB3	NM_001368067.1	MANE Plus Clinical	c.756-21_756-10delCTCTCTCTCTCT		intron	N/A	NP_001354996.1	A0A0S2Z530
	LDB3	NM_001171610.2		c.1100+6686_1100+6697delCTCTCTCTCTCT		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+6680delTCTCTCTCTCTC		intron	N/A	ENSP00000355296.3	O75112-1
	LDB3	ENST00000263066.11	TSL:1 MANE Plus Clinical	c.756-38_756-27delTCTCTCTCTCTC		intron	N/A	ENSP00000263066.7	O75112-6
	ENSG00000289258	ENST00000443292.2	TSL:1	c.2406-38_2406-27delTCTCTCTCTCTC		intron	N/A	ENSP00000393132.2	C9JWU6

Frequencies

GnomAD3 genomes AF: 0.0000740 AC: 11 AN: 148744 Hom.: 0 Cov.: 0

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.: 0 AF XY: 0.000120 AC XY: 85 AN XY: 705828

African (AFR) AF: 0.0000618 AC: 2 AN: 32386

American (AMR) AF: 0.0000225 AC: 1 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.0000514 AC: 2 AN: 38942

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85048

European-Finnish (FIN) AF: 0.0000385 AC: 2 AN: 51956

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5666

European-Non Finnish (NFE) AF: 0.000143 AC: 153 AN: 1071344

Other (OTH) AF: 0.0000512 AC: 3 AN: 58626

GnomAD4 genome AF: 0.0000740 AC: 11 AN: 148744 Hom.: 0 Cov.: 0 AF XY: 0.0000553 AC XY: 4 AN XY: 72356

African (AFR) AF: 0.00 AC: 0 AN: 40380

American (AMR) AF: 0.00 AC: 0 AN: 14944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5022

South Asian (SAS) AF: 0.00 AC: 0 AN: 4596

European-Finnish (FIN) AF: 0.0000989 AC: 1 AN: 10116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.000149 AC: 10 AN: 67010

Other (OTH) AF: 0.00 AC: 0 AN: 2032

Alfa AF: 0.00 Hom.: 224

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	LDB3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71019410; hg19: chr10-88458996;