4-16898413-T-C

Variant names:

• chr4-16898413-T-C
• rs140709141
• NM_001290.5:c.73A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001290.5(LDB2):​c.73A>G​(p.Met25Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: LDB2 NM_001290.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.300039).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

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.73A>G	p.Met25Val	missense	Exon 1 of 8	NP_001281.1	O43679-1
	LDB2	NM_001304434.2		c.73A>G	p.Met25Val	missense	Exon 1 of 8	NP_001291363.1	G5E9Y7
	LDB2	NM_001130834.3		c.73A>G	p.Met25Val	missense	Exon 1 of 9	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.73A>G	p.Met25Val	missense	Exon 1 of 8	ENSP00000306772.5	O43679-1
	LDB2	ENST00000441778.6	TSL:1	c.73A>G	p.Met25Val	missense	Exon 1 of 9	ENSP00000392089.2	O43679-2
	LDB2	ENST00000502640.5	TSL:1	c.73A>G	p.Met25Val	missense	Exon 1 of 8	ENSP00000423963.1	E9PFI4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151996 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251392 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461522 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727084

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111674

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151996 Hom.: 0 Cov.: 27 AF XY: 0.0000270 AC XY: 2 AN XY: 74198

African (AFR) AF: 0.0000725 AC: 3 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000177 Hom.: 0

Bravo AF: 0.0000416

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.18
Sift	Benign	0.51	T
Sift4G	Benign	0.50	T
Polyphen		0.0010	B
Vest4		0.40
MVP		0.49
MPC		0.73
ClinPred		0.14	T
GERP RS		5.0
PromoterAI		-0.013	Neutral
Varity_R		0.21
gMVP		0.88
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140709141; hg19: chr4-16900036;