Variant 2-140234778-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_018557.3(LRP1B):c.13659+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 772,822 control chromosomes in the GnomAD database, including 1,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.049 ( 307 hom., cov: 31)

Exomes 𝑓: 0.063 ( 1677 hom. )

Consequence

LRP1B
NM_018557.3 splice_region, intron

Scores

Splicing: ADA: 0.005132

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.16

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 2-140234778-T-C is Benign according to our data. Variant chr2-140234778-T-C is described in ClinVar as [Benign]. Clinvar id is 3056106.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
LRP1B	NM_018557.3 linkuse as main transcript	c.13659+8A>G	splice_region_variant, intron_variant	ENST00000389484.8
LRP1B	XM_017004341.2 linkuse as main transcript	c.13269+8A>G	splice_region_variant, intron_variant
LRP1B	XM_017004342.1 linkuse as main transcript	c.8511+8A>G	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
LRP1B	ENST00000389484.8 linkuse as main transcript	c.13659+8A>G	splice_region_variant, intron_variant		1	NM_018557.3	P1
	ENST00000622722.1 linkuse as main transcript	n.146A>G	non_coding_transcript_exon_variant	1/1
LRP1B	ENST00000437977.5 linkuse as main transcript	c.2256-1452A>G	intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7371

AN:

151062

Hom.:

309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0642

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.000588

Gnomad SAS

AF:

0.0646

Gnomad FIN

AF:

0.0342

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0642

Gnomad OTH

AF:

0.0829

GnomAD3 exomes

AF:

0.0573

AC:

14043

AN:

245198

Hom.:

594

AF XY:

0.0618

AC XY:

8203

AN XY:

132802

show subpopulations

Gnomad AFR exome

AF:

0.00848

Gnomad AMR exome

AF:

0.0428

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.000221

Gnomad SAS exome

AF:

0.0694

Gnomad FIN exome

AF:

0.0326

Gnomad NFE exome

AF:

0.0667

Gnomad OTH exome

AF:

0.0773

GnomAD4 exome

AF:

0.0626

AC:

38895

AN:

621642

Hom.:

1677

Cov.:

AF XY:

0.0648

AC XY:

21979

AN XY:

339034

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.0450

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.0696

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.0665

Gnomad4 OTH exome

AF:

0.0736

GnomAD4 genome

AF:

0.0488

AC:

7373

AN:

151180

Hom.:

307

Cov.:

AF XY:

0.0491

AC XY:

3628

AN XY:

73868

show subpopulations

Gnomad4 AFR

AF:

0.0106

Gnomad4 AMR

AF:

0.0641

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.000589

Gnomad4 SAS

AF:

0.0657

Gnomad4 FIN

AF:

0.0342

Gnomad4 NFE

AF:

0.0642

Gnomad4 OTH

AF:

0.0825

Alfa

AF:

0.0645

Hom.:

182

Bravo

AF:

0.0498

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

EpiCase

AF:

0.0838

EpiControl

AF:

0.0843

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LRP1B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0051

dbscSNV1_RF

Benign

0.038

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over