chr4-16601133-C-T

Variant names:

• chr4-16601133-C-T
• rs10939673
• NM_001290.5:c.236-5258G>A

Variant summary

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

The NM_001290.5(LDB2):​c.236-5258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,854 control chromosomes in the GnomAD database, including 11,155 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 0.38 (11155 hom., cov: 33)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 2 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]

ENSG00000287081 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 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.236-5258G>A		intron	N/A	NP_001281.1	O43679-1
	LDB2	NM_001304434.2		c.236-5258G>A		intron	N/A	NP_001291363.1	G5E9Y7
	LDB2	NM_001130834.3		c.236-5258G>A		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.236-5258G>A		intron	N/A	ENSP00000306772.5	O43679-1
	LDB2	ENST00000441778.6	TSL:1	c.236-5258G>A		intron	N/A	ENSP00000392089.2	O43679-2
	LDB2	ENST00000502640.5	TSL:1	c.236-5258G>A		intron	N/A	ENSP00000423963.1	E9PFI4

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57069 AN: 151736 Hom.: 11140 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.376 AC: 57133 AN: 151854 Hom.: 11155 Cov.: 33 AF XY: 0.376 AC XY: 27902 AN XY: 74226

African (AFR) AF: 0.283 AC: 11751 AN: 41456

American (AMR) AF: 0.410 AC: 6247 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2943 AN: 5146

South Asian (SAS) AF: 0.477 AC: 2297 AN: 4820

European-Finnish (FIN) AF: 0.376 AC: 3962 AN: 10544

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27452 AN: 67864

Other (OTH) AF: 0.368 AC: 776 AN: 2110

Alfa AF: 0.390 Hom.: 1469

Bravo AF: 0.375

Asia WGS AF: 0.525 AC: 1824 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.65
PhyloP100		-1.3
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: rs10939673; hg19: chr4-16602756;