rs2714212

Positions:

• chr2-141350950-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018557.3(LRP1B):​c.344-96309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,734 control chromosomes in the GnomAD database, including 16,773 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 0.44 (16773 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.344-96309C>T		intron_variant		ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-47-96309C>T		intron_variant			XP_016859830.1
LRP1B	XM_047444771.1	c.455-96309C>T		intron_variant			XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.344-96309C>T		intron_variant		1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.206-368674C>T		intron_variant		2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67432 AN: 151618 Hom.: 16776 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.444 AC: 67437 AN: 151734 Hom.: 16773 Cov.: 32 AF XY: 0.439 AC XY: 32582 AN XY: 74142

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.458

Alfa AF: 0.496 Hom.: 3443

Bravo AF: 0.415

Asia WGS AF: 0.327 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.60

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: rs2714212; hg19: chr2-142108519;