rs11677045

Variant names:

• chr2-141471504-A-G
• rs11677045
• NM_018557.3:c.343+8892T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018557.3(LRP1B):​c.343+8892T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,936 control chromosomes in the GnomAD database, including 6,253 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 0.27 (6253 hom., cov: 30)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• 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]

LOC124906079 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 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.343+8892T>C		intron	N/A	NP_061027.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.343+8892T>C		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000434794.1	TSL:2	c.205+338775T>C		intron	N/A	ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41648 AN: 151818 Hom.: 6248 Cov.: 30

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.274 AC: 41685 AN: 151936 Hom.: 6253 Cov.: 30 AF XY: 0.274 AC XY: 20374 AN XY: 74248

African (AFR) AF: 0.389 AC: 16117 AN: 41426

American (AMR) AF: 0.226 AC: 3459 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3470

East Asian (EAS) AF: 0.164 AC: 848 AN: 5156

South Asian (SAS) AF: 0.419 AC: 2019 AN: 4814

European-Finnish (FIN) AF: 0.227 AC: 2401 AN: 10554

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15328 AN: 67928

Other (OTH) AF: 0.251 AC: 529 AN: 2108

Alfa AF: 0.287 Hom.: 2995

Bravo AF: 0.273

Asia WGS AF: 0.328 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.48
PhyloP100		0.72
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: rs11677045; hg19: chr2-142229073;