rs1496747

Positions:

• chr4-16597611-C-T

Variant summary

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

The NM_001290.5(LDB2):​c.236-1736G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,956 control chromosomes in the GnomAD database, including 20,003 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 0.51 (20003 hom., cov: 33)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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]

LOC124900604 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDB2	NM_001290.5	c.236-1736G>A		intron_variant		ENST00000304523.10
LOC124900604	XR_001741395.2	n.193-659C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDB2	ENST00000304523.10	c.236-1736G>A		intron_variant		1	NM_001290.5	P4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77431 AN: 151838 Hom.: 19995 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.510 AC: 77468 AN: 151956 Hom.: 20003 Cov.: 33 AF XY: 0.511 AC XY: 37901 AN XY: 74234

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.557

Alfa AF: 0.516 Hom.: 27754

Bravo AF: 0.518

Asia WGS AF: 0.417 AC: 1446 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.9
DANN	Benign	0.34

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: rs1496747; hg19: chr4-16599234;