Variant chr2-140274519-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_018557.3(LRP1B):c.13047G>A(p.Thr4349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,611,552 control chromosomes in the GnomAD database, including 348,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.54 ( 24585 hom., cov: 32)

Exomes 𝑓: 0.66 ( 323906 hom. )

Consequence

LRP1B
NM_018557.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.288

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-140274519-C-T is Benign according to our data. Variant chr2-140274519-C-T is described in ClinVar as [Benign]. Clinvar id is 3060762.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.288 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRP1B	NM_018557.3 linkuse as main transcript	c.13047G>A	p.Thr4349=	synonymous_variant	85/91	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2 linkuse as main transcript	c.12657G>A	p.Thr4219=	synonymous_variant	85/91		XP_016859830.1
LRP1B	XM_017004342.1 linkuse as main transcript	c.7899G>A	p.Thr2633=	synonymous_variant	56/62		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRP1B	ENST00000389484.8 linkuse as main transcript	c.13047G>A	p.Thr4349=	synonymous_variant	85/91	1	NM_018557.3	ENSP00000374135	P1
LRP1B	ENST00000437977.5 linkuse as main transcript	c.1743G>A	p.Thr581=	synonymous_variant	12/17	5		ENSP00000415052
LRP1B	ENST00000442974.1 linkuse as main transcript	c.243G>A	p.Thr81=	synonymous_variant	2/7	5		ENSP00000393859

Frequencies

GnomAD3 genomes

AF:

0.536

AC:

81215

AN:

151616

Hom.:

24588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.725

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.608

AC:

152554

AN:

250726

Hom.:

48288

AF XY:

0.615

AC XY:

83369

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.534

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.685

Gnomad SAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.689

Gnomad NFE exome

AF:

0.673

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.660

AC:

963582

AN:

1459820

Hom.:

323906

Cov.:

AF XY:

0.659

AC XY:

478315

AN XY:

726262

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.537

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.669

Gnomad4 SAS exome

AF:

0.580

Gnomad4 FIN exome

AF:

0.681

Gnomad4 NFE exome

AF:

0.689

Gnomad4 OTH exome

AF:

0.627

GnomAD4 genome

AF:

0.535

AC:

81230

AN:

151732

Hom.:

24585

Cov.:

AF XY:

0.537

AC XY:

39771

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.536

Gnomad4 ASJ

AF:

0.536

Gnomad4 EAS

AF:

0.674

Gnomad4 SAS

AF:

0.554

Gnomad4 FIN

AF:

0.702

Gnomad4 NFE

AF:

0.676

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.603

Hom.:

18139

Bravo

AF:

0.512

Asia WGS

AF:

0.563

AC:

1954

AN:

3476

EpiCase

AF:

0.663

EpiControl

AF:

0.657

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LRP1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

-0.54

CADD

Benign

7.8

DANN

Benign

0.61

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