rs11812601

Variant names:

• chr10-86668410-G-A
• rs11812601
• ENST00000443292.2:c.1487-259G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-86668410-G-A
• chr10-86668410-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001368064.1(LDB3):​c.-23-259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 523,250 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: LDB3 NM_001368064.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

Genes affected

ENSG00000289258 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00193 (294/152288) while in subpopulation NFE AF= 0.003 (204/68012). AF 95% confidence interval is 0.00266. There are 0 homozygotes in gnomad4. There are 135 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 294 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB3	NM_007078.3	c.-184G>A		upstream_gene_variant		ENST00000361373.9	NP_009009.1
LDB3	NM_001368067.1	c.-184G>A		upstream_gene_variant		ENST00000263066.11	NP_001354996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289258	ENST00000443292.2	c.1487-259G>A		intron_variant	Intron 11 of 17	1		ENSP00000393132.2
LDB3	ENST00000361373.9	c.-184G>A		upstream_gene_variant		1	NM_007078.3	ENSP00000355296.3
LDB3	ENST00000263066.11	c.-184G>A		upstream_gene_variant		1	NM_001368067.1	ENSP00000263066.7

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 294 AN: 152170 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00300

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00206 AC: 766 AN: 370962 Hom.: 3 Cov.: 0 AF XY: 0.00196 AC XY: 383 AN XY: 195894

Gnomad4 AFR exome AF: 0.000543

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.000174

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00158

Gnomad4 NFE exome AF: 0.00283

Gnomad4 OTH exome AF: 0.00274

GnomAD4 genome AF: 0.00193 AC: 294 AN: 152288 Hom.: 0 Cov.: 34 AF XY: 0.00181 AC XY: 135 AN XY: 74452

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00300

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000538 Hom.: 120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11812601; hg19: chr10-88428167;