Variant rs61742974 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002334.4(LRP4):c.129C>G(p.Thr43Thr) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0860

Variant links:

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]

LRP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
LRP4	NM_002334.4 linkuse as main transcript	c.129C>G	p.Thr43Thr	synonymous_variant	2/38	ENST00000378623.6	NP_002325.2	O75096
LRP4	XM_017017734.2 linkuse as main transcript	c.129C>G	p.Thr43Thr	synonymous_variant	2/39		XP_016873223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP4	ENST00000378623.6 linkuse as main transcript	c.129C>G	p.Thr43Thr	synonymous_variant	2/38	1	NM_002334.4	ENSP00000367888.1		O75096
LRP4	ENST00000534404.1 linkuse as main transcript	c.53-2475C>G		intron_variant		5		ENSP00000434763.1		E9PNJ5

Frequencies

GnomAD3 genomes

AF:

0.0430

AC:

6544

AN:

152138

Hom.:

465

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00375

AC XY:

2727

AN XY:

727224

show subpopulations

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.:

AF XY:

0.0410

AC XY:

3049

AN XY:

74438

show subpopulations

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.:

Bravo

AF:

0.0505

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over