Genetic Variant LRP1B:c.344-91A>G (chr2-141254732-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019): 0P and 12B. BA1BP4_Strong

The NM_018557.3(LRP1B):c.344-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.223 (AC=217,127) in the gnomAD database across 972,638 control chromosomes, including 24,812 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.259. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3532 hom., cov: 32)

Exomes 𝑓: 0.23 ( 21280 hom. )

Consequence

LRP1B
NM_018557.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.266

Publications

6 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.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2591 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.344-91A>G		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.344-91A>G		intron	N/A	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000434794.1	TSL:2	c.206-272456A>G		intron	N/A	ENSP00000413239.1	E7ERG8

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32289

AN:

151892

Hom.:

3520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.214

GnomAD4 exome

AF:

0.225

AC:

184800

AN:

820628

Hom.:

21280

AF XY:

0.226

AC XY:

93309

AN XY:

413292

show subpopulations

African (AFR)

AF:

0.202

AC:

3415

AN:

16904

American (AMR)

AF:

0.202

AC:

2918

AN:

14448

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

3724

AN:

16688

East Asian (EAS)

AF:

0.148

AC:

4171

AN:

28180

South Asian (SAS)

AF:

0.263

AC:

12188

AN:

46344

European-Finnish (FIN)

AF:

0.213

AC:

7665

AN:

35946

Middle Eastern (MID)

AF:

0.208

AC:

554

AN:

2664

European-Non Finnish (NFE)

AF:

0.228

AC:

141782

AN:

622232

Other (OTH)

AF:

0.225

AC:

8383

AN:

37222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

6771

13541

20312

27082

33853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4456

8912

13368

17824

22280

<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:

0.213

AC:

32327

AN:

152010

Hom.:

3532

Cov.:

AF XY:

0.212

AC XY:

15780

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.202

AC:

8380

AN:

41502

American (AMR)

AF:

0.208

AC:

3177

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

743

AN:

3458

East Asian (EAS)

AF:

0.191

AC:

992

AN:

5182

South Asian (SAS)

AF:

0.254

AC:

1227

AN:

4822

European-Finnish (FIN)

AF:

0.223

AC:

2357

AN:

10580

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14705

AN:

67888

Other (OTH)

AF:

0.218

AC:

461

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1297

2593

3890

5186

6483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.219

Hom.:

1777

Bravo

AF:

0.213

Asia WGS

AF:

0.219

AC:

761

AN:

3470

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.132

AC:

16047

AN:

121640

Turkish Variome

AF:

0.220

AC:

340

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.196

AC:

1758

AN:

8960

Hom.:

180

ABraOM SABE-WGS-1171

AF:

0.196

AC:

459

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

(source)

DANN

Benign

0.63

PhyloP100

-0.27

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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chr2 141254732 . T C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over