rs491391

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1B	NM_018557.3	c.6800-2850T>G		intron_variant		ENST00000389484.8
LRP1B	XM_017004341.2	c.6410-2850T>G		intron_variant
LRP1B	XM_017004342.1	c.1652-2850T>G		intron_variant
LRP1B	XM_047444771.1	c.6911-2850T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1B	ENST00000389484.8	c.6800-2850T>G		intron_variant		1	NM_018557.3	P1

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

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0470

Gnomad4 FIN AF: 0.0708

Gnomad4 NFE AF: 0.0566

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0597 Hom.: 553

Bravo AF: 0.0866

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs491391; hg19: chr2-141362058;