rs149906323

chr11-46898566-C-Achr11-46898566-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_002334.4(LRP4):c.788G>T(p.Arg263Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R263H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRP4 NM_002334.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

Genes affected

LRP4 (HGNC:6696): (LDL receptor related protein 4) This gene encodes a member of the low-density lipoprotein receptor-related protein family. The encoded protein may be a regulator of Wnt signaling. Mutations in this gene are associated with Cenani-Lenz syndrome. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, LRP4
• BP4: Computational evidence support a benign effect (MetaRNN=0.4140525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP4	NM_002334.4	c.788G>T	p.Arg263Leu	missense_variant	7/38	ENST00000378623.6
LRP4	XM_017017734.2	c.788G>T	p.Arg263Leu	missense_variant	7/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP4	ENST00000378623.6	c.788G>T	p.Arg263Leu	missense_variant	7/38	1	NM_002334.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251382 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135870

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.24
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.13
Sift	Benign	0.26	T
Sift4G	Benign	0.21	T
Polyphen		0.0020	B
Vest4		0.63
MutPred		0.48		Loss of phosphorylation at S260 (P = 0.1111);
MVP		0.45
MPC		0.68
ClinPred		0.68	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.13
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149906323; hg19: chr11-46920117;