chr4-16512785-C-T

Variant names:

• chr4-16512785-C-T
• rs955943
• NM_001290.5:c.616-681G>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.616-681G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 152,118 control chromosomes in the GnomAD database, including 995 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 0.091 (995 hom., cov: 32)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 4 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]

ENSG00000248138 (HGNC:58741):

LOC105374505 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 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.616-681G>A		intron	N/A	NP_001281.1
	LDB2	NM_001304434.2		c.616-681G>A		intron	N/A	NP_001291363.1
	LDB2	NM_001130834.3		c.616-681G>A		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.616-681G>A		intron	N/A	ENSP00000306772.5
	LDB2	ENST00000441778.6	TSL:1	c.616-681G>A		intron	N/A	ENSP00000392089.2
	LDB2	ENST00000502640.5	TSL:1	c.616-681G>A		intron	N/A	ENSP00000423963.1

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13789 AN: 152000 Hom.: 993 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0908 AC: 13813 AN: 152118 Hom.: 995 Cov.: 32 AF XY: 0.0934 AC XY: 6942 AN XY: 74360

African (AFR) AF: 0.183 AC: 7598 AN: 41444

American (AMR) AF: 0.0859 AC: 1313 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.0521 AC: 270 AN: 5186

South Asian (SAS) AF: 0.0443 AC: 213 AN: 4808

European-Finnish (FIN) AF: 0.0884 AC: 936 AN: 10586

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0457 AC: 3108 AN: 68018

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.0647 Hom.: 1023

Bravo AF: 0.0959

Asia WGS AF: 0.0510 AC: 178 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		-0.055
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: rs955943; hg19: chr4-16514408;