rs13420111

Positions:

• chr2-140823763-A-G

Variant summary

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

The NM_018557.3(LRP1B):​c.5210-9957T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,856 control chromosomes in the GnomAD database, including 1,444 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 0.13 (1444 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.5210-9957T>C		intron_variant		ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.4820-9957T>C		intron_variant			XP_016859830.1
LRP1B	XM_047444771.1	c.5321-9957T>C		intron_variant			XP_047300727.1
LRP1B	XM_017004342.1	c.62-9957T>C		intron_variant			XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.5210-9957T>C		intron_variant		1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19096 AN: 151746 Hom.: 1444 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.0898

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.126 AC: 19103 AN: 151856 Hom.: 1444 Cov.: 32 AF XY: 0.126 AC XY: 9369 AN XY: 74248

Gnomad4 AFR AF: 0.0646

Gnomad4 AMR AF: 0.0896

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.123

Alfa AF: 0.160 Hom.: 1321

Bravo AF: 0.113

Asia WGS AF: 0.0590 AC: 206 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.84

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: rs13420111; hg19: chr2-141581332;