Variant 19-33205520-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002333.4(LRP3):c.750C>T(p.Pro250Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,562,118 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

LRP3
NM_002333.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.72

Variant links:

Genes affected

LRP3 (HGNC:6695): (LDL receptor related protein 3) Involved in negative regulation of fat cell differentiation; positive regulation of osteoblast differentiation; and regulation of gene expression. Predicted to be located in clathrin-coated pit. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRP3 links:

LRP3 (HGNC:):

LRP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-33205520-C-T is Benign according to our data. Variant chr19-33205520-C-T is described in ClinVar as [Benign]. Clinvar id is 729824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.72 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP3	NM_002333.4 linkuse as main transcript	c.750C>T	p.Pro250Pro	synonymous_variant	5/7	ENST00000253193.9	NP_002324.2	O75074
LRP3	XM_005258945.2 linkuse as main transcript	c.750C>T	p.Pro250Pro	synonymous_variant	5/7		XP_005259002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRP3	ENST00000253193.9 linkuse as main transcript	c.750C>T	p.Pro250Pro	synonymous_variant	5/7	1	NM_002333.4	ENSP00000253193.6	O75074
LRP3	ENST00000590275.1 linkuse as main transcript	n.1064C>T		non_coding_transcript_exon_variant	3/3	2
LRP3	ENST00000590278.1 linkuse as main transcript	n.1651C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00377

AC:

574

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00199

AC:

343

AN:

172540

Hom.:

AF XY:

0.00185

AC XY:

176

AN XY:

95094

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00162

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000880

Gnomad OTH exome

AF:

0.00482

GnomAD4 exome

AF:

0.00105

AC:

1484

AN:

1409836

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

736

AN XY:

696826

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.00362

Gnomad4 ASJ exome

AF:

0.00152

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000661

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.00379

AC:

577

AN:

152282

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.00450

Asia WGS

AF:

0.00173

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.075

DANN

Benign

0.92

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