chr2-140274452-T-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018557.3(LRP1B):c.13114A>T(p.Asn4372Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,612,564 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 46 hom. )

Consequence

LRP1B
NM_018557.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.11

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015412033).

BP6

Variant 2-140274452-T-A is Benign according to our data. Variant chr2-140274452-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 772849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00449 (683/152164) while in subpopulation NFE AF= 0.00668 (454/67974). AF 95% confidence interval is 0.00617. There are 2 homozygotes in gnomad4. There are 338 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 683 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3 link	c.13114A>T	p.Asn4372Tyr	missense_variant	Exon 85 of 91	ENST00000389484.8	NP_061027.2	Q9NZR2
LRP1B	XM_017004341.2 link	c.12724A>T	p.Asn4242Tyr	missense_variant	Exon 85 of 91		XP_016859830.1
LRP1B	XM_017004342.1 link	c.7966A>T	p.Asn2656Tyr	missense_variant	Exon 56 of 62		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRP1B	ENST00000389484.8 link	c.13114A>T	p.Asn4372Tyr	missense_variant	Exon 85 of 91	1	NM_018557.3	ENSP00000374135.3	Q9NZR2
LRP1B	ENST00000437977.5 link	c.1807A>T	p.Asn603Tyr	missense_variant	Exon 12 of 17	5		ENSP00000415052.1	H0Y7T7
LRP1B	ENST00000442974.1 link	c.307A>T	p.Asn103Tyr	missense_variant	Exon 2 of 7	5		ENSP00000393859.1	H7C0A8

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

683

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00492

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00668

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00563

AC:

1412

AN:

250716

Hom.:

AF XY:

0.00570

AC XY:

773

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.00401

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00363

Gnomad FIN exome

AF:

0.00676

Gnomad NFE exome

AF:

0.00815

Gnomad OTH exome

AF:

0.00475

GnomAD4 exome

AF:

0.00609

AC:

8893

AN:

1460400

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

4344

AN XY:

726518

show subpopulations

Gnomad4 AFR exome

AF:

0.000719

Gnomad4 AMR exome

AF:

0.00412

Gnomad4 ASJ exome

AF:

0.00514

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00389

Gnomad4 FIN exome

AF:

0.00554

Gnomad4 NFE exome

AF:

0.00673

Gnomad4 OTH exome

AF:

0.00665

GnomAD4 genome

AF:

0.00449

AC:

683

AN:

152164

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

338

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00492

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.00668

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00609

Hom.:

Bravo

AF:

0.00461

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00628

AC:

762

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LRP1B: BP4, BS2 -

LRP1B-related disorder

Benign:1

Mar 06, 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

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

0.081

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

M_CAP

Benign

0.049

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.43

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0020

Polyphen

0.14

Vest4

0.74

MVP

0.58

MPC

0.61

ClinPred

0.023

GERP RS

2.9

Varity_R

0.18

gMVP

0.85

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