Variant rs74806847 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002334.4(LRP4):c.4837+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,614,064 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 164 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 145 hom. )

Consequence

LRP4
NM_002334.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.242

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-46868978-G-A is Benign according to our data. Variant chr11-46868978-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 304854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP4	NM_002334.4 linkuse as main transcript	c.4837+10C>T		intron_variant		ENST00000378623.6
LRP4-AS1	NR_038909.1 linkuse as main transcript	n.198-4096G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
LRP4	ENST00000378623.6 linkuse as main transcript	c.4837+10C>T	intron_variant	1	NM_002334.4	P1
LRP4-AS1	ENST00000502049.3 linkuse as main transcript	n.193-4096G>A	intron_variant, non_coding_transcript_variant	2
LRP4-AS1	ENST00000531719.5 linkuse as main transcript	n.292-4096G>A	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.0254

AC:

3869

AN:

152096

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0884

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00930

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0197

GnomAD3 exomes

AF:

0.00627

AC:

1576

AN:

251366

Hom.:

AF XY:

0.00459

AC XY:

623

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0875

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00243

AC:

3546

AN:

1461850

Hom.:

145

Cov.:

AF XY:

0.00207

AC XY:

1504

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0881

Gnomad4 AMR exome

AF:

0.00438

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000531

Gnomad4 OTH exome

AF:

0.00517

GnomAD4 genome

AF:

0.0255

AC:

3882

AN:

152214

Hom.:

164

Cov.:

AF XY:

0.0241

AC XY:

1796

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0884

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0195

Alfa

AF:

0.0197

Hom.:

Bravo

AF:

0.0288

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cenani-Lenz syndactyly syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 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

-0.80

Cadd

Benign

2.6

Dann

Benign

0.78

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