rs183373550

Variant names:

• chr2-140511873-C-G
• rs183373550
• NM_018557.3:c.8270-1817G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018557.3(LRP1B):​c.8270-1817G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 152,190 control chromosomes in the GnomAD database, including 3 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 0.0034 (3 hom., cov: 33)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• 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=-0.88).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00339 (516/152190) while in subpopulation AMR AF = 0.00647 (99/15292). AF 95% confidence interval is 0.00544. There are 3 homozygotes in GnomAd4. There are 245 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 516 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.8270-1817G>C		intron_variant	Intron 51 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.7880-1817G>C		intron_variant	Intron 51 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.8381-1817G>C		intron_variant	Intron 51 of 76		XP_047300727.1
LRP1B	XM_017004342.1	c.3122-1817G>C		intron_variant	Intron 22 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.8270-1817G>C		intron_variant	Intron 51 of 90	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.00339 AC: 516 AN: 152072 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00802

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00310

Gnomad OTH AF: 0.00670

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

GnomAD4 genome AF: 0.00339 AC: 516 AN: 152190 Hom.: 3 Cov.: 33 AF XY: 0.00329 AC XY: 245 AN XY: 74416

African (AFR) AF: 0.000506 AC: 21 AN: 41534

American (AMR) AF: 0.00647 AC: 99 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00802 AC: 85 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00310 AC: 211 AN: 68002

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.00185 Hom.: 0

Bravo AF: 0.00344

Asia WGS AF: 0.00145 AC: 5 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.50
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism

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: rs183373550; hg19: chr2-141269442;