rs491391

Variant names:

• chr2-140604489-A-C
• rs491391
• NM_018557.3:c.6800-2850T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-140604489-A-C
• chr2-140604489-A-G

Variant summary

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

The NM_018557.3(LRP1B):​c.6800-2850T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0856 in 152,104 control chromosomes in the GnomAD database, including 834 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 0.086 (834 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018557.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.6800-2850T>G		intron	N/A	NP_061027.2	Q9NZR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.6800-2850T>G		intron	N/A	ENSP00000374135.3	Q9NZR2

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13006 AN: 151986 Hom.: 834 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0747

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

GnomAD4 genome AF: 0.0856 AC: 13020 AN: 152104 Hom.: 834 Cov.: 32 AF XY: 0.0848 AC XY: 6306 AN XY: 74362

African (AFR) AF: 0.173 AC: 7187 AN: 41474

American (AMR) AF: 0.0413 AC: 630 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.0470 AC: 227 AN: 4826

European-Finnish (FIN) AF: 0.0708 AC: 751 AN: 10600

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0566 AC: 3847 AN: 67980

Other (OTH) AF: 0.0739 AC: 156 AN: 2110

Alfa AF: 0.0647 Hom.: 1411

Bravo AF: 0.0866

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.81
PhyloP100		0.38
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: rs491391; hg19: chr2-141362058;