4-16529199-A-T

Variant names:

• chr4-16529199-A-T
• rs1160670
• NM_001290.5:c.616-17095T>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.616-17095T>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
• 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]

LOC105374505 (HGNC:):

ENSG00000248138 (HGNC:58741):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB2	NM_001290.5	MANE Select	c.616-17095T>A		intron	N/A	NP_001281.1	O43679-1
	LDB2	NM_001304434.2		c.616-17095T>A		intron	N/A	NP_001291363.1	G5E9Y7
	LDB2	NM_001130834.3		c.616-17095T>A		intron	N/A	NP_001124306.1	O43679-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB2	ENST00000304523.10	TSL:1 MANE Select	c.616-17095T>A		intron	N/A	ENSP00000306772.5	O43679-1
	LDB2	ENST00000441778.6	TSL:1	c.616-17095T>A		intron	N/A	ENSP00000392089.2	O43679-2
	LDB2	ENST00000502640.5	TSL:1	c.616-17095T>A		intron	N/A	ENSP00000423963.1	E9PFI4

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

African (AFR) AF: 0.457 AC: 18933 AN: 41392

American (AMR) AF: 0.332 AC: 5070 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3468

East Asian (EAS) AF: 0.628 AC: 3232 AN: 5148

South Asian (SAS) AF: 0.451 AC: 2160 AN: 4790

European-Finnish (FIN) AF: 0.296 AC: 3123 AN: 10554

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21092 AN: 67958

Other (OTH) AF: 0.361 AC: 762 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.83
PhyloP100		0.0060
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: rs1160670; hg19: chr4-16530822;