rs283015

Positions:

• chr4-16727694-C-G
• chr4-16727694-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290.5(LDB2):​c.235+31464G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,050 control chromosomes in the GnomAD database, including 5,739 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 0.27 (5739 hom., cov: 32)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

LDB2 (HGNC:6533): (LIM domain binding 2) The protein encoded by this gene belongs to the LIM-domain binding family. Members of this family are characterized by a conserved nuclear localization sequence, an amino-terminal homodimerization domain and a carboxy-terminal LIM interaction domain. These proteins function as adapter molecules to allow assembly of transcriptional regulatory complexes. Genetic association studies suggest functions for this gene in rhegmatogenous retinal detachment and coronary artery disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDB2	NM_001290.5	c.235+31464G>C		intron_variant		ENST00000304523.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDB2	ENST00000304523.10	c.235+31464G>C		intron_variant		1	NM_001290.5	P4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40470 AN: 151932 Hom.: 5738 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.266 AC: 40494 AN: 152050 Hom.: 5739 Cov.: 32 AF XY: 0.264 AC XY: 19618 AN XY: 74326

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.266

Alfa AF: 0.175 Hom.: 399

Bravo AF: 0.258

Asia WGS AF: 0.238 AC: 827 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.34

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: rs283015; hg19: chr4-16729317;