rs1483012

Variant names:

• chr4-16892270-G-A
• rs1483012
• NM_001290.5:c.132+6084C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290.5(LDB2):​c.132+6084C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,970 control chromosomes in the GnomAD database, including 20,287 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 0.50 (20287 hom., cov: 32)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290.5. 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
	LDB2	NM_001290.5	MANE Select	c.132+6084C>T		intron	N/A	NP_001281.1	O43679-1
	LDB2	NM_001304434.2		c.132+6084C>T		intron	N/A	NP_001291363.1	G5E9Y7
	LDB2	NM_001130834.3		c.132+6084C>T		intron	N/A	NP_001124306.1	O43679-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB2	ENST00000304523.10	TSL:1 MANE Select	c.132+6084C>T		intron	N/A	ENSP00000306772.5	O43679-1
	LDB2	ENST00000441778.6	TSL:1	c.132+6084C>T		intron	N/A	ENSP00000392089.2	O43679-2
	LDB2	ENST00000502640.5	TSL:1	c.132+6084C>T		intron	N/A	ENSP00000423963.1	E9PFI4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75409 AN: 151852 Hom.: 20245 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.497 AC: 75520 AN: 151970 Hom.: 20287 Cov.: 32 AF XY: 0.493 AC XY: 36602 AN XY: 74266

African (AFR) AF: 0.708 AC: 29335 AN: 41448

American (AMR) AF: 0.488 AC: 7456 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3470

East Asian (EAS) AF: 0.171 AC: 882 AN: 5164

South Asian (SAS) AF: 0.373 AC: 1795 AN: 4814

European-Finnish (FIN) AF: 0.425 AC: 4489 AN: 10550

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28910 AN: 67936

Other (OTH) AF: 0.473 AC: 997 AN: 2108

Alfa AF: 0.462 Hom.: 23449

Bravo AF: 0.509

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		0.083
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1483012; hg19: chr4-16893893;