Genetic Variant LRP1B:p.Cys2774Cys (chr2-140510004-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_018557.3(LRP1B):c.8322C>T(p.Cys2774Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,613,798 control chromosomes in the GnomAD database, including 4,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.059 ( 355 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3647 hom. )

Consequence

LRP1B
NM_018557.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0130

Publications

12 publications found

Variant links:

Genes affected

LRP1B (HGNC:6693): (LDL receptor related protein 1B) This gene encodes a member of the low density lipoprotein (LDL) receptor family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands. Disruption of this gene has been reported in several types of cancer. [provided by RefSeq, Jun 2016]

LRP1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 2-140510004-G-A is Benign according to our data. Variant chr2-140510004-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055616.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.013 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018557.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.8322C>T	p.Cys2774Cys	synonymous	Exon 52 of 91	NP_061027.2	Q9NZR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.8322C>T	p.Cys2774Cys	synonymous	Exon 52 of 91	ENSP00000374135.3	Q9NZR2

Frequencies

GnomAD3 genomes

AF:

0.0592

AC:

8997

AN:

152082

Hom.:

355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0614

Gnomad ASJ

AF:

0.0723

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0334

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0827

Gnomad OTH

AF:

0.0546

GnomAD2 exomes

AF:

0.0570

AC:

14317

AN:

251362

AF XY:

0.0579

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.0729

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0716

Gnomad NFE exome

AF:

0.0782

Gnomad OTH exome

AF:

0.0623

GnomAD4 exome

AF:

0.0650

AC:

94952

AN:

1461598

Hom.:

3647

Cov.:

AF XY:

0.0652

AC XY:

47385

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.0256

AC:

857

AN:

33470

American (AMR)

AF:

0.0371

AC:

1658

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0727

AC:

1901

AN:

26132

East Asian (EAS)

AF:

0.000327

AC:

AN:

39700

South Asian (SAS)

AF:

0.0341

AC:

2943

AN:

86244

European-Finnish (FIN)

AF:

0.0727

AC:

3881

AN:

53412

Middle Eastern (MID)

AF:

0.0542

AC:

305

AN:

5630

European-Non Finnish (NFE)

AF:

0.0718

AC:

79866

AN:

1111916

Other (OTH)

AF:

0.0584

AC:

3528

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4590

9179

13769

18358

22948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2698

5396

8094

10792

13490

<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:

0.0591

AC:

8996

AN:

152200

Hom.:

355

Cov.:

AF XY:

0.0588

AC XY:

4373

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0277

AC:

1152

AN:

41532

American (AMR)

AF:

0.0612

AC:

936

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0723

AC:

251

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.0332

AC:

160

AN:

4818

European-Finnish (FIN)

AF:

0.0685

AC:

726

AN:

10592

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0828

AC:

5627

AN:

67998

Other (OTH)

AF:

0.0545

AC:

115

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

432

863

1295

1726

2158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0661

Hom.:

236

Bravo

AF:

0.0543

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0748

EpiControl

AF:

0.0761

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

LRP1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

4.9

(source)

DANN

Benign

0.58

PhyloP100

-0.013

Mutation Taster

=77/23

polymorphism (auto)

(source)

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

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