rs61742974

Positions:

• chr11-46902853-G-C
• chr11-46902853-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002334.4(LRP4):​c.129C>G​(p.Thr43=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00806 in 1,614,076 control chromosomes in the GnomAD database, including 905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (465 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (440 hom.)
• Consequence: LRP4 NM_002334.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0860

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 11-46902853-G-C is Benign according to our data. Variant chr11-46902853-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 304905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.086 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP4	NM_002334.4	c.129C>G	p.Thr43=	synonymous_variant	2/38	ENST00000378623.6
LRP4	XM_017017734.2	c.129C>G	p.Thr43=	synonymous_variant	2/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP4	ENST00000378623.6	c.129C>G	p.Thr43=	synonymous_variant	2/38	1	NM_002334.4	P1
LRP4	ENST00000534404.1	c.53-2475C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6544 AN: 152138 Hom.: 465 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0177

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0296

GnomAD3 exomes AF: 0.0117 AC: 2940 AN: 251372 Hom.: 211 AF XY: 0.00846 AC XY: 1149 AN XY: 135892

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.00879

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00442 AC: 6455 AN: 1461820 Hom.: 440 Cov.: 32 AF XY: 0.00375 AC XY: 2727 AN XY: 727224

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.00957

Gnomad4 ASJ exome AF: 0.00149

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0430 AC: 6553 AN: 152256 Hom.: 465 Cov.: 32 AF XY: 0.0410 AC XY: 3049 AN XY: 74438

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0177

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.00302 Hom.: 13

Bravo AF: 0.0505

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cenani-Lenz syndactyly syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cenani-Lenz syndactyly syndrome;C3280402:Sclerosteosis 2;C4225377:Congenital myasthenic syndrome 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.6
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

LitVar

Other links and lift over

dbSNP: rs61742974; hg19: chr11-46924404;