rs11886422

Variant names:

• chr2-141388632-G-A
• rs11886422
• NM_018557.3:c.343+91764C>T

Variant summary

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

The NM_018557.3(LRP1B):​c.343+91764C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 152,108 control chromosomes in the GnomAD database, including 514 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 0.071 (514 hom., cov: 33)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.343+91764C>T		intron_variant	Intron 3 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-48+91764C>T		intron_variant	Intron 3 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.454+91764C>T		intron_variant	Intron 3 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.343+91764C>T		intron_variant	Intron 3 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.206-406356C>T		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10829 AN: 151990 Hom.: 512 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.0835

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0517

Gnomad OTH AF: 0.0638

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

GnomAD4 genome AF: 0.0713 AC: 10847 AN: 152108 Hom.: 514 Cov.: 33 AF XY: 0.0702 AC XY: 5218 AN XY: 74352

African (AFR) AF: 0.127 AC: 5250 AN: 41470

American (AMR) AF: 0.0512 AC: 782 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3468

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5164

South Asian (SAS) AF: 0.0836 AC: 403 AN: 4822

European-Finnish (FIN) AF: 0.0193 AC: 204 AN: 10580

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0517 AC: 3513 AN: 68004

Other (OTH) AF: 0.0636 AC: 134 AN: 2106

Alfa AF: 0.0558 Hom.: 36

Bravo AF: 0.0750

Asia WGS AF: 0.0580 AC: 199 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.12
PhyloP100		-1.7
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: rs11886422; hg19: chr2-142146201;