chr2-141084351-T-C

Variant names:

• chr2-141084351-T-C
• rs2049480
• NM_018557.3:c.1014-22078A>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.1014-22078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,986 control chromosomes in the GnomAD database, including 18,960 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 0.48 (18960 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.1014-22078A>G		intron_variant	Intron 7 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.624-22078A>G		intron_variant	Intron 7 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.1125-22078A>G		intron_variant	Intron 7 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.1014-22078A>G		intron_variant	Intron 7 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.206-102075A>G		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73645 AN: 151866 Hom.: 18962 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.485 AC: 73663 AN: 151986 Hom.: 18960 Cov.: 32 AF XY: 0.478 AC XY: 35509 AN XY: 74272

African (AFR) AF: 0.335 AC: 13874 AN: 41474

American (AMR) AF: 0.513 AC: 7830 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2279 AN: 3472

East Asian (EAS) AF: 0.235 AC: 1211 AN: 5148

South Asian (SAS) AF: 0.462 AC: 2226 AN: 4818

European-Finnish (FIN) AF: 0.480 AC: 5058 AN: 10542

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.580 AC: 39405 AN: 67952

Other (OTH) AF: 0.525 AC: 1106 AN: 2108

Alfa AF: 0.549 Hom.: 72988

Bravo AF: 0.476

Asia WGS AF: 0.365 AC: 1269 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.72
PhyloP100		-0.21
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: rs2049480; hg19: chr2-141841920;