Variant rs1012672 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002336.3(LRP6):c.3810C>T(p.Cys1270Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 1,613,826 control chromosomes in the GnomAD database, including 3,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 309 hom., cov: 31)

Exomes 𝑓: 0.067 ( 3589 hom. )

Consequence

LRP6
NM_002336.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.763

Variant links:

Genes affected

LRP6 (HGNC:6698): (LDL receptor related protein 6) This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands. The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby transmits the canonical Wnt/beta-catenin signaling cascade. Through its interaction with the Wnt/beta-catenin signaling cascade this gene plays a role in the regulation of cell differentiation, proliferation, and migration and the development of many cancer types. This protein undergoes gamma-secretase dependent RIP- (regulated intramembrane proteolysis) processing but the precise locations of the cleavage sites have not been determined.[provided by RefSeq, Dec 2009]

LRP6 links:

LRP6 (HGNC:):

LRP6 links:

BCL2L14 (HGNC:16657): (BCL2 like 14) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Overexpression of this gene has been shown to induce apoptosis in cells. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported for this gene. [provided by RefSeq, May 2009]

BCL2L14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 12-12131981-G-A is Benign according to our data. Variant chr12-12131981-G-A is described in ClinVar as [Benign]. Clinvar id is 1237676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.763 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP6	NM_002336.3 linkuse as main transcript	c.3810C>T	p.Cys1270Cys	synonymous_variant	18/23	ENST00000261349.9	NP_002327.2	O75581

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP6	ENST00000261349.9 linkuse as main transcript	c.3810C>T	p.Cys1270Cys	synonymous_variant	18/23	1	NM_002336.3	ENSP00000261349.4		O75581

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8696

AN:

151962

Hom.:

310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0342

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.0541

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.0231

Gnomad FIN

AF:

0.0806

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0696

Gnomad OTH

AF:

0.0768

GnomAD3 exomes

AF:

0.0590

AC:

14826

AN:

251216

Hom.:

552

AF XY:

0.0597

AC XY:

8099

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.0453

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.0124

Gnomad SAS exome

AF:

0.0343

Gnomad FIN exome

AF:

0.0793

Gnomad NFE exome

AF:

0.0702

Gnomad OTH exome

AF:

0.0808

GnomAD4 exome

AF:

0.0670

AC:

97947

AN:

1461746

Hom.:

3589

Cov.:

AF XY:

0.0663

AC XY:

48245

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0347

Gnomad4 AMR exome

AF:

0.0481

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.0302

Gnomad4 SAS exome

AF:

0.0339

Gnomad4 FIN exome

AF:

0.0792

Gnomad4 NFE exome

AF:

0.0700

Gnomad4 OTH exome

AF:

0.0713

GnomAD4 genome

AF:

0.0572

AC:

8703

AN:

152080

Hom.:

309

Cov.:

AF XY:

0.0576

AC XY:

4285

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0343

Gnomad4 AMR

AF:

0.0540

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.0172

Gnomad4 SAS

AF:

0.0239

Gnomad4 FIN

AF:

0.0806

Gnomad4 NFE

AF:

0.0696

Gnomad4 OTH

AF:

0.0760

Alfa

AF:

0.0695

Hom.:

661

Bravo

AF:

0.0566

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0750

EpiControl

AF:

0.0759

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 17, 2020	This variant is associated with the following publications: (PMID: 17517621) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.32

DANN

Benign

0.81

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