4-16529199-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290.5(LDB2):c.616-17095T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,896 control chromosomes in the GnomAD database, including 10,724 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 0.37 (10724 hom., cov: 31)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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]

LOC105374505 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDB2	NM_001290.5	c.616-17095T>A		intron_variant		ENST00000304523.10
LOC105374505	XR_007058068.1	n.209-7431A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDB2	ENST00000304523.10	c.616-17095T>A		intron_variant		1	NM_001290.5	P4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55677 AN: 151778 Hom.: 10715 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.367 AC: 55719 AN: 151896 Hom.: 10724 Cov.: 31 AF XY: 0.367 AC XY: 27228 AN XY: 74212

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.361

Alfa AF: 0.176 Hom.: 346

Bravo AF: 0.373

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs1160670; hg19: chr4-16530822;