Genetic Variant LRP1B:c.206-7845G>A (chr2-141488378-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018557.3(LRP1B):c.206-7845G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,946 control chromosomes in the GnomAD database, including 14,892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14892 hom., cov: 31)

Consequence

LRP1B
NM_018557.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.29

Publications

9 publications found

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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new If you want to explore the variant's impact on the transcript NM_018557.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

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.206-7845G>A		intron	N/A	NP_061027.2	Q9NZR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.206-7845G>A		intron	N/A	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000434794.1	TSL:2	c.205+321901G>A		intron	N/A	ENSP00000413239.1	E7ERG8

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64251

AN:

151828

Hom.:

14888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.647

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.423

AC:

64279

AN:

151946

Hom.:

14892

Cov.:

AF XY:

0.430

AC XY:

31943

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.235

AC:

9759

AN:

41456

American (AMR)

AF:

0.485

AC:

7394

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1778

AN:

3470

East Asian (EAS)

AF:

0.708

AC:

3657

AN:

5164

South Asian (SAS)

AF:

0.647

AC:

3117

AN:

4814

European-Finnish (FIN)

AF:

0.457

AC:

4819

AN:

10548

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32313

AN:

67930

Other (OTH)

AF:

0.447

AC:

943

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1798

3597

5395

7194

8992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.464

Hom.:

54994

Bravo

AF:

0.416

Asia WGS

AF:

0.628

AC:

2184

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

(source)

DANN

Benign

0.56

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over