Genetic Variant NM_018557.3:c.13659+10G>T (chr2-140234776-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_018557.3(LRP1B):c.13659+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000781 in 771,908 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

LRP1B
NM_018557.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.803

Publications

0 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:

ENSG00000277306 (HGNC:):

ENSG00000277306 links:

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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=-0.38).

BP6

Variant 2-140234776-C-A is Benign according to our data. Variant chr2-140234776-C-A is described in ClinVar as Benign. ClinVar VariationId is 719459.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00261 (395/151178) while in subpopulation AFR AF = 0.0089 (368/41370). AF 95% confidence interval is 0.00815. There are 2 homozygotes in GnomAd4. There are 188 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 395 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.13659+10G>T		intron	N/A	NP_061027.2	Q9NZR2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.13659+10G>T	intron	N/A	ENSP00000374135.3	Q9NZR2
LRP1B	ENST00000437977.5	TSL:5	c.2254-1450G>T	intron	N/A	ENSP00000415052.1	H0Y7T7
ENSG00000277306	ENST00000622722.1	TSL:6	n.148G>T	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

396

AN:

151060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00895

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.000966

GnomAD2 exomes

AF:

0.000695

AC:

170

AN:

244570

AF XY:

0.000536

show subpopulations

Gnomad AFR exome

AF:

0.00931

Gnomad AMR exome

AF:

0.000355

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000823

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000335

AC:

208

AN:

620730

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

AN XY:

338584

show subpopulations

African (AFR)

AF:

0.00824

AC:

142

AN:

17232

American (AMR)

AF:

0.000559

AC:

AN:

42896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20594

East Asian (EAS)

AF:

0.00

AC:

AN:

35788

South Asian (SAS)

AF:

0.00

AC:

AN:

69062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52862

Middle Eastern (MID)

AF:

0.000739

AC:

AN:

4058

European-Non Finnish (NFE)

AF:

0.0000579

AC:

AN:

345698

Other (OTH)

AF:

0.000584

AC:

AN:

32540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00261

AC:

395

AN:

151178

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

188

AN XY:

73832

show subpopulations

African (AFR)

AF:

0.00890

AC:

368

AN:

41370

American (AMR)

AF:

0.00146

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5082

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

67468

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00159

Hom.:

Bravo

AF:

0.00298

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.80

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