chr4-16759189-T-C

Variant names:

• chr4-16759189-T-C
• rs35508244
• NM_001290.5:c.204A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001290.5(LDB2):​c.204A>G​(p.Ser68Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,613,890 control chromosomes in the GnomAD database, including 271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (140 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (131 hom.)
• Consequence: LDB2 NM_001290.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.444
• Publications: 3 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 4-16759189-T-C is Benign according to our data. Variant chr4-16759189-T-C is described in ClinVar as Benign. ClinVar VariationId is 784036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.444 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0757 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.204A>G	p.Ser68Ser	synonymous	Exon 2 of 8	NP_001281.1	O43679-1
	LDB2	NM_001304434.2		c.204A>G	p.Ser68Ser	synonymous	Exon 2 of 8	NP_001291363.1	G5E9Y7
	LDB2	NM_001130834.3		c.204A>G	p.Ser68Ser	synonymous	Exon 2 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.204A>G	p.Ser68Ser	synonymous	Exon 2 of 8	ENSP00000306772.5	O43679-1
	LDB2	ENST00000441778.6	TSL:1	c.204A>G	p.Ser68Ser	synonymous	Exon 2 of 9	ENSP00000392089.2	O43679-2
	LDB2	ENST00000502640.5	TSL:1	c.204A>G	p.Ser68Ser	synonymous	Exon 2 of 8	ENSP00000423963.1	E9PFI4

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3432 AN: 152090 Hom.: 137 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00910

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.00587 AC: 1474 AN: 251258 AF XY: 0.00404

Gnomad AFR exome AF: 0.0793

Gnomad AMR exome AF: 0.00364

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00236 AC: 3445 AN: 1461682 Hom.: 131 Cov.: 30 AF XY: 0.00209 AC XY: 1521 AN XY: 727166

African (AFR) AF: 0.0788 AC: 2638 AN: 33462

American (AMR) AF: 0.00416 AC: 186 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5768

European-Non Finnish (NFE) AF: 0.000210 AC: 233 AN: 1111842

Other (OTH) AF: 0.00546 AC: 330 AN: 60386

GnomAD4 genome AF: 0.0226 AC: 3446 AN: 152208 Hom.: 140 Cov.: 32 AF XY: 0.0223 AC XY: 1657 AN XY: 74426

African (AFR) AF: 0.0779 AC: 3236 AN: 41524

American (AMR) AF: 0.00909 AC: 139 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68016

Other (OTH) AF: 0.0180 AC: 38 AN: 2110

Alfa AF: 0.0101 Hom.: 33

Bravo AF: 0.0253

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.7
DANN	Benign	0.63
PhyloP100		-0.44
Mutation Taster		=96/4	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: rs35508244; hg19: chr4-16760812;