rs12474609

Variant names:

• chr2-140963573-A-T
• rs12474609
• NM_018557.3:c.2888-11633T>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.2888-11633T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,096 control chromosomes in the GnomAD database, including 2,604 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 0.18 (2604 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.2888-11633T>A		intron_variant	Intron 18 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.2498-11633T>A		intron_variant	Intron 18 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.2999-11633T>A		intron_variant	Intron 18 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.2888-11633T>A		intron_variant	Intron 18 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.323-11633T>A		intron_variant	Intron 3 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27571 AN: 151978 Hom.: 2597 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.181 AC: 27596 AN: 152096 Hom.: 2604 Cov.: 32 AF XY: 0.183 AC XY: 13572 AN XY: 74362

African (AFR) AF: 0.214 AC: 8868 AN: 41484

American (AMR) AF: 0.165 AC: 2517 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3470

East Asian (EAS) AF: 0.245 AC: 1264 AN: 5160

South Asian (SAS) AF: 0.245 AC: 1184 AN: 4824

European-Finnish (FIN) AF: 0.161 AC: 1701 AN: 10570

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11025 AN: 67988

Other (OTH) AF: 0.165 AC: 349 AN: 2112

Alfa AF: 0.169 Hom.: 1260

Bravo AF: 0.183

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.65
PhyloP100		0.18
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: rs12474609; hg19: chr2-141721142;