Variant chr2-140274596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_018557.3(LRP1B):c.12970G>A(p.Val4324Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,604,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LRP1B
NM_018557.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37606925).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRP1B	NM_018557.3 linkuse as main transcript	c.12970G>A	p.Val4324Met	missense_variant, splice_region_variant	85/91	ENST00000389484.8
LRP1B	XM_017004341.2 linkuse as main transcript	c.12580G>A	p.Val4194Met	missense_variant, splice_region_variant	85/91
LRP1B	XM_017004342.1 linkuse as main transcript	c.7822G>A	p.Val2608Met	missense_variant, splice_region_variant	56/62

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRP1B	ENST00000389484.8 linkuse as main transcript	c.12970G>A	p.Val4324Met	missense_variant, splice_region_variant	85/91	1	NM_018557.3	P1
LRP1B	ENST00000437977.5 linkuse as main transcript	c.1666G>A	p.Val556Met	missense_variant, splice_region_variant	12/17	5
LRP1B	ENST00000442974.1 linkuse as main transcript	c.166G>A	p.Val56Met	missense_variant, splice_region_variant	2/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

151696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000368

AC:

AN:

244570

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132202

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000389

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1452500

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

722212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000228

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000659

AC:

AN:

151814

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000453

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

M_CAP

Benign

0.078

MetaRNN

Benign

0.38

MetaSVM

Uncertain

0.37

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.90

PrimateAI

Benign

0.45

PROVEAN

Benign

0.24

REVEL

Uncertain

0.38

Sift

Benign

0.17

Sift4G

Benign

0.21

Polyphen

0.98

Vest4

0.47

MutPred

0.60

Loss of stability (P = 0.3677);

MVP

0.24

MPC

0.49

ClinPred

0.11

GERP RS

5.4

Varity_R

0.089

gMVP

0.18

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