NM_007078.3:c.896+6694_896+6697delCTCT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000289258 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3	c.896+6694_896+6697delCTCT		intron_variant	Intron 7 of 13	ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.756-13_756-10delCTCT		intron_variant	Intron 8 of 8	ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDB3	ENST00000361373.9	c.896+6669_896+6672delTCTC		intron_variant	Intron 7 of 13	1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.756-38_756-35delTCTC		intron_variant	Intron 8 of 8	1	NM_001368067.1	ENSP00000263066.7
ENSG00000289258	ENST00000443292.2	c.2406-38_2406-35delTCTC		intron_variant	Intron 17 of 17	1		ENSP00000393132.2

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

GnomAD3 exomes AF: 0.138 AC: 31104 AN: 225518 Hom.: 24 AF XY: 0.136 AC XY: 16780 AN XY: 123426

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 SAS exome AF: 0.0942

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

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0355

Gnomad4 SAS exome AF: 0.0797

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.125

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

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0638

Gnomad4 ASJ AF: 0.0407

Gnomad4 EAS AF: 0.0248

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.0966

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jul 14, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 12, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

756-15_756-12delCTCT in intron 7 of LDB3: This variant is not expected to have c linical significance because it is not located in the conserved +/- 1, 2 region of the splicing consensus sequence. -

not provided Benign:1

Aug 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs71019410; hg19: chr10-88458996;