Variant 2-140297947-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_018557.3(LRP1B):c.12828A>C(p.Ala4276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,612,388 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

LRP1B
NM_018557.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.64

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-140297947-T-G is Benign according to our data. Variant chr2-140297947-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3039093.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-4.64 with no splicing effect.

BS2

High AC in GnomAd4 at 195 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRP1B	NM_018557.3 linkuse as main transcript	c.12828A>C	p.Ala4276=	synonymous_variant	84/91	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2 linkuse as main transcript	c.12438A>C	p.Ala4146=	synonymous_variant	84/91		XP_016859830.1
LRP1B	XM_017004342.1 linkuse as main transcript	c.7680A>C	p.Ala2560=	synonymous_variant	55/62		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRP1B	ENST00000389484.8 linkuse as main transcript	c.12828A>C	p.Ala4276=	synonymous_variant	84/91	1	NM_018557.3	ENSP00000374135	P1
LRP1B	ENST00000437977.5 linkuse as main transcript	c.1524A>C	p.Ala508=	synonymous_variant	11/17	5		ENSP00000415052
LRP1B	ENST00000442974.1 linkuse as main transcript	c.24A>C	p.Ala8=	synonymous_variant	1/7	5		ENSP00000393859

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00142

AC:

355

AN:

250696

Hom.:

AF XY:

0.00140

AC XY:

190

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00194

AC:

2833

AN:

1460088

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1350

AN XY:

726214

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00237

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152300

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00113

EpiCase

AF:

0.00247

EpiControl

AF:

0.00137

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LRP1B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 2019

This variant is classified as likely 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

-0.85

CADD

Benign

0.26

DANN

Benign

0.54

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