chr2-140246960-A-G

Variant names:

• chr2-140246960-A-G
• rs2129483
• NM_018557.3:c.13324+126T>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.13324+126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 632,904 control chromosomes in the GnomAD database, including 280,688 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 0.91 (62736 hom., cov: 33)
  • Exomes 𝑓: 0.95 (217952 hom.)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.13324+126T>C		intron	N/A	NP_061027.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.13324+126T>C		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000437977.5	TSL:5	c.2017+126T>C		intron	N/A	ENSP00000415052.1
	LRP1B	ENST00000442974.1	TSL:5	c.631+126T>C		intron	N/A	ENSP00000393859.1

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137161 AN: 151524 Hom.: 62708 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.927

GnomAD4 exome AF: 0.951 AC: 457612 AN: 481262 Hom.: 217952 AF XY: 0.950 AC XY: 244166 AN XY: 256938

African (AFR) AF: 0.762 AC: 10184 AN: 13360

American (AMR) AF: 0.964 AC: 27592 AN: 28626

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 14814 AN: 15324

East Asian (EAS) AF: 0.957 AC: 27937 AN: 29200

South Asian (SAS) AF: 0.922 AC: 45647 AN: 49494

European-Finnish (FIN) AF: 0.970 AC: 31576 AN: 32542

Middle Eastern (MID) AF: 0.938 AC: 2871 AN: 3060

European-Non Finnish (NFE) AF: 0.961 AC: 273298 AN: 284478

Other (OTH) AF: 0.941 AC: 23693 AN: 25178

GnomAD4 genome AF: 0.905 AC: 137241 AN: 151642 Hom.: 62736 Cov.: 33 AF XY: 0.906 AC XY: 67094 AN XY: 74094

African (AFR) AF: 0.765 AC: 31699 AN: 41432

American (AMR) AF: 0.949 AC: 14387 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 3345 AN: 3462

East Asian (EAS) AF: 0.975 AC: 4998 AN: 5128

South Asian (SAS) AF: 0.916 AC: 4415 AN: 4822

European-Finnish (FIN) AF: 0.972 AC: 10327 AN: 10624

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.960 AC: 64986 AN: 67706

Other (OTH) AF: 0.926 AC: 1951 AN: 2106

Alfa AF: 0.936 Hom.: 34033

Bravo AF: 0.898

Asia WGS AF: 0.925 AC: 3216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.49
PhyloP100		-1.6
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: rs2129483; hg19: chr2-141004529;