chr2-141120932-C-A

Variant names:

• chr2-141120932-C-A
• rs12691592
• NM_018557.3:c.1014-58659G>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.1014-58659G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,814 control chromosomes in the GnomAD database, including 6,792 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 0.29 (6792 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.1014-58659G>T		intron_variant	Intron 7 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.624-58659G>T		intron_variant	Intron 7 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.1125-58659G>T		intron_variant	Intron 7 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.1014-58659G>T		intron_variant	Intron 7 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.206-138656G>T		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44540 AN: 151696 Hom.: 6774 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.294 AC: 44601 AN: 151814 Hom.: 6792 Cov.: 32 AF XY: 0.302 AC XY: 22365 AN XY: 74174

African (AFR) AF: 0.257 AC: 10665 AN: 41476

American (AMR) AF: 0.326 AC: 4955 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 674 AN: 3462

East Asian (EAS) AF: 0.478 AC: 2463 AN: 5150

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4816

European-Finnish (FIN) AF: 0.403 AC: 4252 AN: 10550

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19421 AN: 67832

Other (OTH) AF: 0.280 AC: 590 AN: 2106

Alfa AF: 0.290 Hom.: 3152

Bravo AF: 0.289

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.70
PhyloP100		-0.28
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: rs12691592; hg19: chr2-141878501; COSMIC: COSV107496545;