2-142050747-G-C

Variant names:

• chr2-142050747-G-C
• rs1449504
• NM_018557.3:c.82+79901C>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.82+79901C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,838 control chromosomes in the GnomAD database, including 16,038 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 0.43 (16038 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018557.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.82+79901C>G		intron	N/A	NP_061027.2	Q9NZR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.82+79901C>G		intron	N/A	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000434794.1	TSL:2	c.82+79901C>G		intron	N/A	ENSP00000413239.1	E7ERG8

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65488 AN: 151720 Hom.: 16033 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.431 AC: 65485 AN: 151838 Hom.: 16038 Cov.: 32 AF XY: 0.435 AC XY: 32283 AN XY: 74164

African (AFR) AF: 0.185 AC: 7683 AN: 41448

American (AMR) AF: 0.570 AC: 8680 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1490 AN: 3464

East Asian (EAS) AF: 0.685 AC: 3519 AN: 5134

South Asian (SAS) AF: 0.402 AC: 1933 AN: 4808

European-Finnish (FIN) AF: 0.524 AC: 5504 AN: 10506

Middle Eastern (MID) AF: 0.348 AC: 101 AN: 290

European-Non Finnish (NFE) AF: 0.517 AC: 35154 AN: 67938

Other (OTH) AF: 0.444 AC: 935 AN: 2104

Alfa AF: 0.343 Hom.: 1016

Bravo AF: 0.427

Asia WGS AF: 0.470 AC: 1631 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.46
PhyloP100		-0.81
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: rs1449504; hg19: chr2-142808316;