chr4-16725163-A-C

Variant names:

• chr4-16725163-A-C
• rs2658509
• NM_001290.5:c.235+33995T>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.235+33995T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,912 control chromosomes in the GnomAD database, including 17,549 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 0.47 (17549 hom., cov: 31)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB2	NM_001290.5	MANE Select	c.235+33995T>G		intron	N/A	NP_001281.1
	LDB2	NM_001304434.2		c.235+33995T>G		intron	N/A	NP_001291363.1
	LDB2	NM_001130834.3		c.235+33995T>G		intron	N/A	NP_001124306.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB2	ENST00000304523.10	TSL:1 MANE Select	c.235+33995T>G		intron	N/A	ENSP00000306772.5
	LDB2	ENST00000441778.6	TSL:1	c.235+33995T>G		intron	N/A	ENSP00000392089.2
	LDB2	ENST00000502640.5	TSL:1	c.235+33995T>G		intron	N/A	ENSP00000423963.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71897 AN: 151794 Hom.: 17526 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.474 AC: 71964 AN: 151912 Hom.: 17549 Cov.: 31 AF XY: 0.481 AC XY: 35721 AN XY: 74230

African (AFR) AF: 0.380 AC: 15735 AN: 41456

American (AMR) AF: 0.520 AC: 7930 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3462

East Asian (EAS) AF: 0.807 AC: 4147 AN: 5140

South Asian (SAS) AF: 0.427 AC: 2058 AN: 4818

European-Finnish (FIN) AF: 0.579 AC: 6095 AN: 10532

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33166 AN: 67940

Other (OTH) AF: 0.459 AC: 969 AN: 2110

Alfa AF: 0.465 Hom.: 10240

Bravo AF: 0.472

Asia WGS AF: 0.609 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		-0.30
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: rs2658509; hg19: chr4-16726786;