rs2075241

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002336.3(LRP6):c.3398-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,609,070 control chromosomes in the GnomAD database, including 24,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2846 hom., cov: 31)

Exomes 𝑓: 0.17 ( 21630 hom. )

Consequence

LRP6
NM_002336.3 intron

Scores

Splicing: ADA: 0.01568

Clinical Significance

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

Conservation

PhyloP100: 0.616

Publications

17 publications found

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:

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-12138545-G-C is Benign according to our data. Variant chr12-12138545-G-C is described in ClinVar as Benign. ClinVar VariationId is 1181344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002336.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRP6	NM_002336.3	MANE Select	c.3398-11C>G	intron	N/A	NP_002327.2	O75581
LRP6	NM_001414244.1		c.3491-11C>G	intron	N/A	NP_001401173.1
LRP6	NM_001414245.1		c.3398-11C>G	intron	N/A	NP_001401174.1	O75581

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRP6	ENST00000261349.9	TSL:1 MANE Select	c.3398-11C>G	intron	N/A	ENSP00000261349.4	O75581
LRP6	ENST00000543091.1	TSL:1	c.3398-11C>G	intron	N/A	ENSP00000442472.1	F5H7J9
LRP6	ENST00000538239.5	TSL:1	n.2990-11C>G	intron	N/A	ENSP00000445083.1	H0YGW5

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28551

AN:

151818

Hom.:

2843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.0970

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.180

GnomAD2 exomes

AF:

0.175

AC:

43881

AN:

250572

AF XY:

0.175

show subpopulations

Gnomad AFR exome

AF:

0.242

Gnomad AMR exome

AF:

0.211

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.0918

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.168

AC:

245303

AN:

1457134

Hom.:

21630

Cov.:

AF XY:

0.170

AC XY:

123038

AN XY:

725248

show subpopulations

African (AFR)

AF:

0.242

AC:

8081

AN:

33392

American (AMR)

AF:

0.205

AC:

9156

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

6179

AN:

26102

East Asian (EAS)

AF:

0.0914

AC:

3623

AN:

39650

South Asian (SAS)

AF:

0.207

AC:

17870

AN:

86134

European-Finnish (FIN)

AF:

0.112

AC:

5971

AN:

53390

Middle Eastern (MID)

AF:

0.237

AC:

1366

AN:

5752

European-Non Finnish (NFE)

AF:

0.165

AC:

182543

AN:

1107764

Other (OTH)

AF:

0.175

AC:

10514

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

9905

19810

29714

39619

49524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6502

13004

19506

26008

32510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.188

AC:

28579

AN:

151936

Hom.:

2846

Cov.:

AF XY:

0.183

AC XY:

13614

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.245

AC:

10120

AN:

41390

American (AMR)

AF:

0.177

AC:

2708

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

812

AN:

3470

East Asian (EAS)

AF:

0.0968

AC:

500

AN:

5164

South Asian (SAS)

AF:

0.198

AC:

954

AN:

4816

European-Finnish (FIN)

AF:

0.111

AC:

1173

AN:

10558

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11674

AN:

67966

Other (OTH)

AF:

0.180

AC:

380

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1172

2344

3517

4689

5861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.185

Hom.:

495

Bravo

AF:

0.196

Asia WGS

AF:

0.159

AC:

554

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.016

dbscSNV1_RF

Benign

0.21

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over