2-142044372-T-C

Variant names:

• chr2-142044372-T-C
• rs2029142
• NM_018557.3:c.82+86276A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018557.3(LRP1B):​c.82+86276A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,412 control chromosomes in the GnomAD database, including 22,434 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 0.54 (22434 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 5 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.82+86276A>G		intron_variant	Intron 1 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-309+64488A>G		intron_variant	Intron 1 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.193+86276A>G		intron_variant	Intron 1 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.82+86276A>G		intron_variant	Intron 1 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.82+86276A>G		intron_variant	Intron 1 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81037 AN: 151294 Hom.: 22416 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.536 AC: 81085 AN: 151412 Hom.: 22434 Cov.: 31 AF XY: 0.539 AC XY: 39889 AN XY: 73958

African (AFR) AF: 0.398 AC: 16452 AN: 41356

American (AMR) AF: 0.623 AC: 9436 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1828 AN: 3456

East Asian (EAS) AF: 0.688 AC: 3505 AN: 5098

South Asian (SAS) AF: 0.416 AC: 1999 AN: 4810

European-Finnish (FIN) AF: 0.656 AC: 6912 AN: 10540

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39224 AN: 67710

Other (OTH) AF: 0.531 AC: 1112 AN: 2096

Alfa AF: 0.557 Hom.: 15619

Bravo AF: 0.530

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.66
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.38		Position offset: -45

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2029142; hg19: chr2-142801941;