NM_018557.3:c.82+60309G>T

Variant names:

• chr2-142070339-C-A
• rs1449477
• NM_018557.3:c.82+60309G>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.82+60309G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,516 control chromosomes in the GnomAD database, including 15,890 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 (15890 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.82+60309G>T		intron	N/A	NP_061027.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.82+60309G>T		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000434794.1	TSL:2	c.82+60309G>T		intron	N/A	ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64791 AN: 151400 Hom.: 15881 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.428 AC: 64794 AN: 151516 Hom.: 15890 Cov.: 32 AF XY: 0.432 AC XY: 31991 AN XY: 74040

African (AFR) AF: 0.174 AC: 7218 AN: 41398

American (AMR) AF: 0.567 AC: 8599 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1507 AN: 3458

East Asian (EAS) AF: 0.687 AC: 3519 AN: 5120

South Asian (SAS) AF: 0.410 AC: 1969 AN: 4804

European-Finnish (FIN) AF: 0.526 AC: 5538 AN: 10528

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 34935 AN: 67744

Other (OTH) AF: 0.443 AC: 932 AN: 2106

Alfa AF: 0.470 Hom.: 8304

Bravo AF: 0.422

Asia WGS AF: 0.473 AC: 1644 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		-0.22
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: rs1449477; hg19: chr2-142827908;