rs2052910

Variant names:

• chr2-140956076-A-C
• rs2052910
• NM_018557.3:c.2888-4136T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-140956076-A-C
• chr2-140956076-A-G
• chr2-140956076-A-T

Variant summary

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

The NM_018557.3(LRP1B):​c.2888-4136T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,466 control chromosomes in the GnomAD database, including 28,807 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 0.60 (28807 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.2888-4136T>G		intron_variant	Intron 18 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.2498-4136T>G		intron_variant	Intron 18 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.2999-4136T>G		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.2888-4136T>G		intron_variant	Intron 18 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.323-4136T>G		intron_variant	Intron 3 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90175 AN: 151348 Hom.: 28793 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.595 AC: 90190 AN: 151466 Hom.: 28807 Cov.: 31 AF XY: 0.601 AC XY: 44486 AN XY: 74032

African (AFR) AF: 0.354 AC: 14657 AN: 41436

American (AMR) AF: 0.690 AC: 10482 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2193 AN: 3460

East Asian (EAS) AF: 0.522 AC: 2695 AN: 5164

South Asian (SAS) AF: 0.613 AC: 2942 AN: 4802

European-Finnish (FIN) AF: 0.734 AC: 7761 AN: 10576

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47354 AN: 67526

Other (OTH) AF: 0.591 AC: 1239 AN: 2098

Alfa AF: 0.662 Hom.: 34079

Bravo AF: 0.579

Asia WGS AF: 0.568 AC: 1971 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.54
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2052910; hg19: chr2-141713645;