rs1496747

Variant names:

• chr4-16597611-C-T
• rs1496747
• NM_001290.5:c.236-1736G>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.236-1736G>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
• 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]

ENSG00000248138 (HGNC:58741):

LOC124900604 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB2	NM_001290.5	c.236-1736G>A		intron_variant	Intron 2 of 7	ENST00000304523.10	NP_001281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDB2	ENST00000304523.10	c.236-1736G>A		intron_variant	Intron 2 of 7	1	NM_001290.5	ENSP00000306772.5

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

African (AFR) AF: 0.529 AC: 21955 AN: 41470

American (AMR) AF: 0.540 AC: 8248 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2148 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1912 AN: 5154

South Asian (SAS) AF: 0.469 AC: 2266 AN: 4828

European-Finnish (FIN) AF: 0.456 AC: 4802 AN: 10520

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34314 AN: 67932

Other (OTH) AF: 0.557 AC: 1174 AN: 2108

Alfa AF: 0.517 Hom.: 34631

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
PhyloP100		0.58
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: rs1496747; hg19: chr4-16599234;