10-86699239-TTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTCTCTCTC

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_007078.3(LDB3):​c.896+6694_896+6697dupCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: LDB3 NM_007078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0920
• 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 -6 ACMG points.

• BP6: Variant 10-86699239-T-TTCTC is Benign according to our data. Variant chr10-86699239-T-TTCTC is described in ClinVar as Benign. ClinVar VariationId is 177829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00153 (227/148850) while in subpopulation AMR AF = 0.00508 (76/14962). AF 95% confidence interval is 0.00416. There are 1 homozygotes in GnomAd4. There are 138 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+6694_896+6697dupCTCT		intron	N/A	NP_009009.1	O75112-1
	LDB3	NM_001368067.1	MANE Plus Clinical	c.756-13_756-10dupCTCT		intron	N/A	NP_001354996.1	A0A0S2Z530
	LDB3	NM_001171610.2		c.1100+6694_1100+6697dupCTCT		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+6668_896+6669insTCTC		intron	N/A	ENSP00000355296.3	O75112-1
	LDB3	ENST00000263066.11	TSL:1 MANE Plus Clinical	c.756-39_756-38insTCTC		intron	N/A	ENSP00000263066.7	O75112-6
	ENSG00000289258	ENST00000443292.2	TSL:1	c.2406-39_2406-38insTCTC		intron	N/A	ENSP00000393132.2	C9JWU6

Frequencies

GnomAD3 genomes AF: 0.00153 AC: 227 AN: 148742 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00508

Gnomad ASJ AF: 0.000872

Gnomad EAS AF: 0.000996

Gnomad SAS AF: 0.000653

Gnomad FIN AF: 0.00346

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00142

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00105 AC: 1478 AN: 1413986 Hom.: 0 Cov.: 0 AF XY: 0.00105 AC XY: 743 AN XY: 705810

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

African (AFR) AF: 0.000339 AC: 11 AN: 32414

American (AMR) AF: 0.00169 AC: 75 AN: 44392

Ashkenazi Jewish (ASJ) AF: 0.000390 AC: 10 AN: 25652

East Asian (EAS) AF: 0.00133 AC: 52 AN: 38966

South Asian (SAS) AF: 0.00131 AC: 111 AN: 85004

European-Finnish (FIN) AF: 0.00245 AC: 127 AN: 51934

Middle Eastern (MID) AF: 0.00106 AC: 6 AN: 5666

European-Non Finnish (NFE) AF: 0.000959 AC: 1027 AN: 1071318

Other (OTH) AF: 0.00101 AC: 59 AN: 58640

⚠️ 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: 0.00153 AC: 227 AN: 148850 Hom.: 1 Cov.: 0 AF XY: 0.00190 AC XY: 138 AN XY: 72470

African (AFR) AF: 0.000247 AC: 10 AN: 40496

American (AMR) AF: 0.00508 AC: 76 AN: 14962

Ashkenazi Jewish (ASJ) AF: 0.000872 AC: 3 AN: 3442

East Asian (EAS) AF: 0.000998 AC: 5 AN: 5010

South Asian (SAS) AF: 0.000653 AC: 3 AN: 4592

European-Finnish (FIN) AF: 0.00346 AC: 35 AN: 10112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00142 AC: 95 AN: 67002

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.00114 Hom.: 224

Bravo AF: 0.00130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.092
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;