rs7671482

Variant names:

• chr4-16895501-A-C
• rs7671482
• NM_001290.5:c.132+2853T>G

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+2853T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,972 control chromosomes in the GnomAD database, including 12,703 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 0.41 (12703 hom., cov: 32)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.442 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+2853T>G		intron	N/A	NP_001281.1
	LDB2	NM_001304434.2		c.132+2853T>G		intron	N/A	NP_001291363.1
	LDB2	NM_001130834.3		c.132+2853T>G		intron	N/A	NP_001124306.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB2	ENST00000304523.10	TSL:1 MANE Select	c.132+2853T>G		intron	N/A	ENSP00000306772.5
	LDB2	ENST00000441778.6	TSL:1	c.132+2853T>G		intron	N/A	ENSP00000392089.2
	LDB2	ENST00000502640.5	TSL:1	c.132+2853T>G		intron	N/A	ENSP00000423963.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61583 AN: 151854 Hom.: 12682 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.406 AC: 61655 AN: 151972 Hom.: 12703 Cov.: 32 AF XY: 0.405 AC XY: 30053 AN XY: 74290

African (AFR) AF: 0.395 AC: 16351 AN: 41410

American (AMR) AF: 0.451 AC: 6882 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3472

East Asian (EAS) AF: 0.170 AC: 881 AN: 5184

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4824

European-Finnish (FIN) AF: 0.425 AC: 4489 AN: 10552

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.423 AC: 28749 AN: 67934

Other (OTH) AF: 0.407 AC: 862 AN: 2116

Alfa AF: 0.413 Hom.: 4238

Bravo AF: 0.405

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.73
PhyloP100		0.19
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: rs7671482; hg19: chr4-16897124;