Variant 11-46856879-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_002334.4(LRP4):c.*2104C>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0197 in 152,270 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.020 ( 101 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRP4
NM_002334.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.14

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 11-46856879-G-C is Benign according to our data. Variant chr11-46856879-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 304825.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0664 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.*2104C>G		3_prime_UTR_variant	38/38	ENST00000378623.6
LRP4-AS1	NR_038909.1 linkuse as main transcript	n.197+10162G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
LRP4	ENST00000378623.6 linkuse as main transcript	c.*2104C>G	3_prime_UTR_variant	38/38	1	NM_002334.4	P1
LRP4-AS1	ENST00000502049.3 linkuse as main transcript	n.192+10162G>C	intron_variant, non_coding_transcript_variant		2
LRP4	ENST00000529604.1 linkuse as main transcript	n.2765C>G	non_coding_transcript_exon_variant	2/2	2
LRP4-AS1	ENST00000531719.5 linkuse as main transcript	n.291+3933G>C	intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2987

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0683

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0139

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

438

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

264

Gnomad4 AFR exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0197

AC:

3003

AN:

152270

Hom.:

101

Cov.:

AF XY:

0.0188

AC XY:

1401

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0685

Gnomad4 AMR

AF:

0.00752

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.89

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