rs2046563

Variant names:

• chr2-140323228-C-A
• rs2046563
• NM_018557.3:c.12514+665G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000300471 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.12514+665G>T		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.12514+665G>T		intron	N/A	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000437977.5	TSL:5	c.1207+665G>T		intron	N/A	ENSP00000415052.1	H0Y7T7
	ENSG00000300471	ENST00000772126.1		n.138+938C>A		intron	N/A

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

African (AFR) AF: 0.346 AC: 14320 AN: 41432

American (AMR) AF: 0.365 AC: 5546 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1110 AN: 5156

South Asian (SAS) AF: 0.343 AC: 1655 AN: 4822

European-Finnish (FIN) AF: 0.535 AC: 5638 AN: 10536

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36075 AN: 67806

Other (OTH) AF: 0.415 AC: 875 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.39
DANN	Benign	0.44
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2046563; hg19: chr2-141080797;