rs2046563

chr2-140323228-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018557.3(LRP1B):c.12514+665G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,736 control chromosomes in the GnomAD database, including 15,613 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 0.44 (15613 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1B	NM_018557.3	c.12514+665G>T		intron_variant		ENST00000389484.8
LRP1B	XM_017004341.2	c.12124+665G>T		intron_variant
LRP1B	XM_017004342.1	c.7366+665G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1B	ENST00000389484.8	c.12514+665G>T		intron_variant		1	NM_018557.3	P1
LRP1B	ENST00000437977.5	c.1209+665G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67163 AN: 151618 Hom.: 15600 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.443 AC: 67217 AN: 151736 Hom.: 15613 Cov.: 32 AF XY: 0.437 AC XY: 32417 AN XY: 74124

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.415

Alfa AF: 0.497 Hom.: 4242

Bravo AF: 0.427

Asia WGS AF: 0.283 AC: 980 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.39
Dann	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs2046563; hg19: chr2-141080797;