Genetic Variant LRP1B:p.Arg4350Cys (chr2-140274518-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018557.3(LRP1B):c.13048C>T(p.Arg4350Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,612,190 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LRP1B
NM_018557.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.30

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3 link	c.13048C>T	p.Arg4350Cys	missense_variant	Exon 85 of 91	ENST00000389484.8	NP_061027.2	Q9NZR2
LRP1B	XM_017004341.2 link	c.12658C>T	p.Arg4220Cys	missense_variant	Exon 85 of 91		XP_016859830.1
LRP1B	XM_017004342.1 link	c.7900C>T	p.Arg2634Cys	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.13048C>T	p.Arg4350Cys	missense_variant	Exon 85 of 91	1	NM_018557.3	ENSP00000374135.3	Q9NZR2
LRP1B	ENST00000437977.5 link	c.1741C>T	p.Arg581Cys	missense_variant	Exon 12 of 17	5		ENSP00000415052.1	H0Y7T7
LRP1B	ENST00000442974.1 link	c.241C>T	p.Arg81Cys	missense_variant	Exon 2 of 7	5		ENSP00000393859.1	H7C0A8

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250854

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460384

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

0.70

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.5

REVEL

Pathogenic

0.75

Sift

Benign

0.057

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.64

MVP

0.38

MPC

0.64

ClinPred

0.85

GERP RS

5.4

Varity_R

0.20

gMVP

0.82

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over