2-141470940-C-T

Variant names:

• chr2-141470940-C-T
• rs12472911
• NM_018557.3:c.343+9456G>A

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+9456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,090 control chromosomes in the GnomAD database, including 37,201 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 0.69 (37201 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.71
• Publications: 22 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 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+9456G>A		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.343+9456G>A		intron	N/A	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000434794.1	TSL:2	c.205+339339G>A		intron	N/A	ENSP00000413239.1	E7ERG8

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104226 AN: 151974 Hom.: 37181 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.686 AC: 104294 AN: 152090 Hom.: 37201 Cov.: 32 AF XY: 0.687 AC XY: 51128 AN XY: 74370

African (AFR) AF: 0.472 AC: 19586 AN: 41454

American (AMR) AF: 0.757 AC: 11574 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2706 AN: 3468

East Asian (EAS) AF: 0.834 AC: 4320 AN: 5178

South Asian (SAS) AF: 0.581 AC: 2798 AN: 4816

European-Finnish (FIN) AF: 0.773 AC: 8194 AN: 10594

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52623 AN: 67982

Other (OTH) AF: 0.718 AC: 1516 AN: 2112

Alfa AF: 0.750 Hom.: 68356

Bravo AF: 0.680

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.015
DANN	Benign	0.41
PhyloP100		-3.7
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: rs12472911; hg19: chr2-142228509;