rs10928113

Positions:

• chr2-141626818-G-A
• chr2-141626818-G-C
• chr2-141626818-G-T

Variant summary

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

The NM_018557.3(LRP1B):​c.206-146285C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,140 control chromosomes in the GnomAD database, including 41,239 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 0.73 (41239 hom., cov: 33)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

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]

LOC107985779 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.206-146285C>T		intron_variant		ENST00000389484.8	NP_061027.2
LOC107985779	XR_007087247.1	n.154+15217G>A		intron_variant, non_coding_transcript_variant
LRP1B	XM_017004341.2	c.-185-146285C>T		intron_variant			XP_016859830.1
LRP1B	XM_047444771.1	c.317-146285C>T		intron_variant			XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.206-146285C>T		intron_variant		1	NM_018557.3	ENSP00000374135	P1
LRP1B	ENST00000434794.1	c.205+183461C>T		intron_variant		2		ENSP00000413239

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110811 AN: 152022 Hom.: 41214 Cov.: 33

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.729 AC: 110884 AN: 152140 Hom.: 41239 Cov.: 33 AF XY: 0.728 AC XY: 54145 AN XY: 74370

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.751

Alfa AF: 0.778 Hom.: 55816

Bravo AF: 0.727

Asia WGS AF: 0.709 AC: 2463 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.56

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: rs10928113; hg19: chr2-142384387;