dbSNP rs898604: LRP4:c.923-97C>T (chr11-46896432-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_002334.4(LRP4):c.923-97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,497,470 control chromosomes in the GnomAD database, including 497,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44816 hom., cov: 33)

Exomes 𝑓: 0.81 ( 452201 hom. )

Consequence

LRP4
NM_002334.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.373

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 11-46896432-G-A is Benign according to our data. Variant chr11-46896432-G-A is described in ClinVar as [Benign]. Clinvar id is 1227084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LRP4	NM_002334.4 link	c.923-97C>T	intron_variant	Intron 8 of 37	ENST00000378623.6	NP_002325.2	O75096
LRP4	XM_017017734.2 link	c.923-97C>T	intron_variant	Intron 8 of 38		XP_016873223.1
LRP4	XM_011520103.3 link	c.119-97C>T	intron_variant	Intron 2 of 31		XP_011518405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP4	ENST00000378623.6 link	c.923-97C>T		intron_variant	Intron 8 of 37	1	NM_002334.4	ENSP00000367888.1		O75096

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115512

AN:

152028

Hom.:

44793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.901

Gnomad AMR

AF:

0.711

Gnomad ASJ

AF:

0.896

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.793

GnomAD4 exome

AF:

0.814

AC:

1094744

AN:

1345324

Hom.:

452201

AF XY:

0.814

AC XY:

548214

AN XY:

673198

show subpopulations

Gnomad4 AFR exome

AF:

0.680

Gnomad4 AMR exome

AF:

0.592

Gnomad4 ASJ exome

AF:

0.898

Gnomad4 EAS exome

AF:

0.374

Gnomad4 SAS exome

AF:

0.770

Gnomad4 FIN exome

AF:

0.774

Gnomad4 NFE exome

AF:

0.847

Gnomad4 OTH exome

AF:

0.809

GnomAD4 genome

AF:

0.760

AC:

115585

AN:

152146

Hom.:

44816

Cov.:

AF XY:

0.752

AC XY:

55981

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.672

Gnomad4 AMR

AF:

0.711

Gnomad4 ASJ

AF:

0.896

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.768

Gnomad4 FIN

AF:

0.743

Gnomad4 NFE

AF:

0.844

Gnomad4 OTH

AF:

0.796

Alfa

AF:

0.832

Hom.:

89340

Bravo

AF:

0.749

Asia WGS

AF:

0.650

AC:

2262

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.6

DANN

Benign

0.68

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