dbSNP rs373757: LRP1B:c.344-91A>G (chr2-141254732-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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 frequency of 0.223 in 972,638 control chromosomes in the GnomAD database, including 24,812 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 0.21 ( 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:

Genome browser will be placed here

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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3 link	c.344-91A>G	intron_variant	Intron 3 of 90	ENST00000389484.8	NP_061027.2	Q9NZR2
LRP1B	XM_017004341.2 link	c.-47-91A>G	intron_variant	Intron 3 of 90		XP_016859830.1
LRP1B	XM_047444771.1 link	c.455-91A>G	intron_variant	Intron 3 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8 link	c.344-91A>G		intron_variant	Intron 3 of 90	1	NM_018557.3	ENSP00000374135.3		Q9NZR2
LRP1B	ENST00000434794.1 link	c.206-272456A>G		intron_variant	Intron 2 of 13	2		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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over