rs16855058

Variant names:

• chr2-141549610-C-T
• rs16855058
• NM_018557.3:c.206-69077G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018557.3(LRP1B):​c.206-69077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 152,104 control chromosomes in the GnomAD database, including 536 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 0.077 (536 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.206-69077G>A		intron_variant	Intron 2 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-185-69077G>A		intron_variant	Intron 2 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.317-69077G>A		intron_variant	Intron 2 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.206-69077G>A		intron_variant	Intron 2 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.205+260669G>A		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11640 AN: 151986 Hom.: 531 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0788

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.0890

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

GnomAD4 genome AF: 0.0766 AC: 11650 AN: 152104 Hom.: 536 Cov.: 32 AF XY: 0.0754 AC XY: 5604 AN XY: 74356

African (AFR) AF: 0.0355 AC: 1472 AN: 41518

American (AMR) AF: 0.0786 AC: 1199 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 244 AN: 3466

East Asian (EAS) AF: 0.0682 AC: 352 AN: 5158

South Asian (SAS) AF: 0.112 AC: 540 AN: 4816

European-Finnish (FIN) AF: 0.0661 AC: 699 AN: 10580

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0996 AC: 6770 AN: 67990

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

Alfa AF: 0.0901 Hom.: 831

Bravo AF: 0.0745

Asia WGS AF: 0.110 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.55
PhyloP100		-3.4
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: rs16855058; hg19: chr2-142307179;