chr11-46871557-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002334.4(LRP4):c.4660A>G(p.Ser1554Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,610,966 control chromosomes in the GnomAD database, including 218,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1554N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.43 ( 15960 hom., cov: 31)

Exomes 𝑓: 0.52 ( 202719 hom. )

Consequence

LRP4
NM_002334.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 7.42

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:

LRP4-AS1 (HGNC:44128): (LRP4 antisense RNA 1)

LRP4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026289523).

BP6

Variant 11-46871557-T-C is Benign according to our data. Variant chr11-46871557-T-C is described in ClinVar as [Benign]. Clinvar id is 304855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP4	NM_002334.4 link	c.4660A>G	p.Ser1554Gly	missense_variant	Exon 31 of 38	ENST00000378623.6	NP_002325.2	O75096

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRP4	ENST00000378623.6 link	c.4660A>G	p.Ser1554Gly	missense_variant	Exon 31 of 38	1	NM_002334.4	ENSP00000367888.1	O75096
LRP4	ENST00000527656.1 link	n.592A>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
LRP4-AS1	ENST00000502049.3 link	n.193-1517T>C		intron_variant	Intron 2 of 2	2
LRP4-AS1	ENST00000531719.5 link	n.292-1517T>C		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64975

AN:

151950

Hom.:

15955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.578

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.462

GnomAD2 exomes

AF:

0.481

AC:

118848

AN:

247302

AF XY:

0.492

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.408

Gnomad ASJ exome

AF:

0.544

Gnomad EAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.585

Gnomad NFE exome

AF:

0.547

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.521

AC:

760306

AN:

1458896

Hom.:

202719

Cov.:

AF XY:

0.523

AC XY:

379363

AN XY:

725626

show subpopulations

Gnomad4 AFR exome

AF:

0.167

AC:

5603

AN:

33456

Gnomad4 AMR exome

AF:

0.420

AC:

18686

AN:

44482

Gnomad4 ASJ exome

AF:

0.540

AC:

14096

AN:

26082

Gnomad4 EAS exome

AF:

0.255

AC:

10090

AN:

39622

Gnomad4 SAS exome

AF:

0.517

AC:

44382

AN:

85820

Gnomad4 FIN exome

AF:

0.589

AC:

31390

AN:

53286

Gnomad4 NFE exome

AF:

0.543

AC:

602851

AN:

1110134

Gnomad4 Remaining exome

AF:

0.506

AC:

30495

AN:

60250

Heterozygous variant carriers

18901

37801

56702

75602

94503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

16772

33544

50316

67088

83860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.427

AC:

64974

AN:

152070

Hom.:

15960

Cov.:

AF XY:

0.429

AC XY:

31918

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.182

AC:

0.182007

AN:

0.182007

Gnomad4 AMR

AF:

0.462

AC:

0.461624

AN:

0.461624

Gnomad4 ASJ

AF:

0.543

AC:

0.543228

AN:

0.543228

Gnomad4 EAS

AF:

0.257

AC:

0.256673

AN:

0.256673

Gnomad4 SAS

AF:

0.528

AC:

0.528263

AN:

0.528263

Gnomad4 FIN

AF:

0.578

AC:

0.577513

AN:

0.577513

Gnomad4 NFE

AF:

0.542

AC:

0.542288

AN:

0.542288

Gnomad4 OTH

AF:

0.468

AC:

0.467803

AN:

0.467803

Heterozygous variant carriers

1697

3394

5091

6788

8485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.502

Hom.:

48042

Bravo

AF:

0.405

TwinsUK

AF:

0.553

AC:

2052

ALSPAC

AF:

0.535

AC:

2063

ESP6500AA

AF:

0.195

AC:

858

ESP6500EA

AF:

0.543

AC:

4671

ExAC

AF:

0.477

AC:

57937

Asia WGS

AF:

0.425

AC:

1481

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cenani-Lenz syndactyly syndrome

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23321396, 21121903) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital myasthenic syndrome 17

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sclerosteosis 2

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.62

Sift

Benign

0.032

Sift4G

Benign

0.10

Polyphen

0.23

Vest4

0.24

MPC

0.57

ClinPred

0.043

GERP RS

5.8

Varity_R

0.20

gMVP

0.48

Mutation Taster

=80/20

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

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