rs12476507

chr2-141136325-A-Gchr2-141136325-A-T

Variant summary

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

The NM_018557.3(LRP1B):c.1013+52096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,566 control chromosomes in the GnomAD database, including 10,757 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 0.36 (10757 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1B	NM_018557.3	c.1013+52096T>C		intron_variant		ENST00000389484.8
LRP1B	XM_017004341.2	c.623+52096T>C		intron_variant
LRP1B	XM_047444771.1	c.1124+52096T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1B	ENST00000389484.8	c.1013+52096T>C		intron_variant		1	NM_018557.3	P1
LRP1B	ENST00000434794.1	c.206-154049T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53868 AN: 151446 Hom.: 10750 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.356 AC: 53897 AN: 151566 Hom.: 10757 Cov.: 31 AF XY: 0.346 AC XY: 25632 AN XY: 74042

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.387

Alfa AF: 0.447 Hom.: 32182

Bravo AF: 0.358

Asia WGS AF: 0.287 AC: 995 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	13
Dann	Benign	0.85

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: rs12476507; hg19: chr2-141893894;