rs2129483

Positions:

• chr2-140246960-A-G
• chr2-140246960-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000389484.8(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 ENST00000389484.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.13324+126T>C		intron_variant		ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.12934+126T>C		intron_variant			XP_016859830.1
LRP1B	XM_017004342.1	c.8176+126T>C		intron_variant			XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.13324+126T>C		intron_variant		1	NM_018557.3	ENSP00000374135	P1
LRP1B	ENST00000437977.5	c.2019+126T>C		intron_variant		5		ENSP00000415052
LRP1B	ENST00000442974.1	c.633+126T>C		intron_variant		5		ENSP00000393859

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

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.964

Gnomad4 ASJ exome AF: 0.967

Gnomad4 EAS exome AF: 0.957

Gnomad4 SAS exome AF: 0.922

Gnomad4 FIN exome AF: 0.970

Gnomad4 NFE exome AF: 0.961

Gnomad4 OTH exome AF: 0.941

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

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.949

Gnomad4 ASJ AF: 0.966

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.960

Gnomad4 OTH AF: 0.926

Alfa AF: 0.936 Hom.: 30258

Bravo AF: 0.898

Asia WGS AF: 0.925 AC: 3216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2129483; hg19: chr2-141004529;