11-46898941-G-T

Variant names:

• chr11-46898941-G-T
• NM_002334.4:c.639C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002334.4(LRP4):​c.639C>A​(p.Asp213Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRP4 NM_002334.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP4	NM_002334.4	c.639C>A	p.Asp213Glu	missense_variant	Exon 6 of 38	ENST00000378623.6	NP_002325.2
LRP4	XM_017017734.2	c.639C>A	p.Asp213Glu	missense_variant	Exon 6 of 39		XP_016873223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP4	ENST00000378623.6	c.639C>A	p.Asp213Glu	missense_variant	Exon 6 of 38	1	NM_002334.4	ENSP00000367888.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461550 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	0.032
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	0.95	L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.53
Sift	Benign	0.10	T
Sift4G	Benign	0.24	T
Polyphen		0.035	B
Vest4		0.65
MutPred		0.63		Gain of disorder (P = 0.2503);
MVP		0.72
MPC		0.73
ClinPred		0.85	D
GERP RS		-3.5
Varity_R		0.13
gMVP		0.63

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-46920492;