Genetic Variant LRP1B:p.Ter4600Ter (chr2-140233187-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018557.3(LRP1B):c.13799A>G(p.Ter4600Ter) variant causes a stop retained change. The variant allele was found at a frequency of 0.000332 in 1,586,566 control chromosomes in the GnomAD database, including 2 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 0.00025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

LRP1B
NM_018557.3 stop_retained

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.95

Publications

0 publications found

Variant links:

COSMIC-nc: COSV104431765

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:

ENSG00000300471 (HGNC:):

ENSG00000300471 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 2-140233187-T-C is Benign according to our data. Variant chr2-140233187-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3053649.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000251 (38/151430) while in subpopulation NFE AF = 0.000385 (26/67530). AF 95% confidence interval is 0.000269. There are 1 homozygotes in GnomAd4. There are 15 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 38 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018557.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.13799A>G	p.Ter4600Ter	stop_retained	Exon 91 of 91	NP_061027.2	Q9NZR2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.13799A>G	p.Ter4600Ter	stop_retained	Exon 91 of 91	ENSP00000374135.3	Q9NZR2
LRP1B	ENST00000437977.5	TSL:5	c.2393A>G	p.Ter798Ter	stop_retained	Exon 17 of 17	ENSP00000415052.1	H0Y7T7
ENSG00000300471	ENST00000772126.1		n.104+8309T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

151312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000400

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000259

AC:

AN:

242904

AF XY:

0.000312

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.000207

Gnomad EAS exome

AF:

0.0000566

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000389

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.000340

AC:

488

AN:

1435136

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

234

AN XY:

715140

show subpopulations

African (AFR)

AF:

0.000123

AC:

AN:

32466

American (AMR)

AF:

0.000161

AC:

AN:

43550

Ashkenazi Jewish (ASJ)

AF:

0.000431

AC:

AN:

25512

East Asian (EAS)

AF:

0.00

AC:

AN:

39074

South Asian (SAS)

AF:

0.000438

AC:

AN:

84450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52412

Middle Eastern (MID)

AF:

0.00301

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.000352

AC:

385

AN:

1092788

Other (OTH)

AF:

0.000456

AC:

AN:

59240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000251

AC:

AN:

151430

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

73978

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41468

American (AMR)

AF:

0.000132

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.000196

AC:

AN:

5100

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000385

AC:

AN:

67530

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000449

Hom.:

Bravo

AF:

0.000200

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

LRP1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.7

(source)

DANN

Benign

0.68

PhyloP100

6.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over