rs574456

Variant names:

• chr2-140644133-A-T
• rs574456
• NM_018557.3:c.6800-42494T>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.6800-42494T>A variant causes a intron change. The variant allele was found at a frequency of 0.0819 in 152,130 control chromosomes in the GnomAD database, including 661 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 0.082 (661 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63
• 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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.6800-42494T>A		intron_variant	Intron 41 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.6410-42494T>A		intron_variant	Intron 41 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.6911-42494T>A		intron_variant	Intron 41 of 76		XP_047300727.1
LRP1B	XM_017004342.1	c.1652-42494T>A		intron_variant	Intron 12 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.6800-42494T>A		intron_variant	Intron 41 of 90	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12434 AN: 152010 Hom.: 658 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0819 AC: 12461 AN: 152130 Hom.: 661 Cov.: 32 AF XY: 0.0847 AC XY: 6302 AN XY: 74382

African (AFR) AF: 0.131 AC: 5433 AN: 41486

American (AMR) AF: 0.117 AC: 1787 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3472

East Asian (EAS) AF: 0.179 AC: 926 AN: 5164

South Asian (SAS) AF: 0.0677 AC: 326 AN: 4816

European-Finnish (FIN) AF: 0.0668 AC: 708 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0428 AC: 2909 AN: 68002

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0596 Hom.: 51

Bravo AF: 0.0906

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		3.6
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: rs574456; hg19: chr2-141401702;