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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3 link	c.8322C>T	p.Cys2774Cys	synonymous_variant	Exon 52 of 91	ENST00000389484.8	NP_061027.2	Q9NZR2
LRP1B	XM_017004341.2 link	c.7932C>T	p.Cys2644Cys	synonymous_variant	Exon 52 of 91		XP_016859830.1
LRP1B	XM_047444771.1 link	c.8433C>T	p.Cys2811Cys	synonymous_variant	Exon 52 of 77		XP_047300727.1
LRP1B	XM_017004342.1 link	c.3174C>T	p.Cys1058Cys	synonymous_variant	Exon 23 of 62		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8 link	c.8322C>T	p.Cys2774Cys	synonymous_variant	Exon 52 of 91	1	NM_018557.3	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

GnomAD3 exomes

AF:

0.0570

AC:

14317

AN:

251362

Hom.:

568

AF XY:

0.0579

AC XY:

7869

AN XY:

135874

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 SAS exome

AF:

0.0344

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

Gnomad4 AFR exome

AF:

0.0256

Gnomad4 AMR exome

AF:

0.0371

Gnomad4 ASJ exome

AF:

0.0727

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0341

Gnomad4 FIN exome

AF:

0.0727

Gnomad4 NFE exome

AF:

0.0718

Gnomad4 OTH exome

AF:

0.0584

GnomAD4 genome

AF:

0.0591

AC:

8996

AN:

152200

Hom.:

355

Cov.:

AF XY:

0.0588

AC XY:

4373

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.0612

Gnomad4 ASJ

AF:

0.0723

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0332

Gnomad4 FIN

AF:

0.0685

Gnomad4 NFE

AF:

0.0828

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0719

Hom.:

231

Bravo

AF:

0.0543

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0748

EpiControl

AF:

0.0761

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LRP1B-related disorder

Benign:1

Dec 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

4.9

DANN

Benign

0.58

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