chr2-141249093-G-T

Variant names:

• chr2-141249093-G-T
• rs9287315
• NM_018557.3:c.464-1739C>A

Variant summary

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

The NM_018557.3(LRP1B):​c.464-1739C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,054 control chromosomes in the GnomAD database, including 6,203 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 0.27 (6203 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 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.464-1739C>A		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.464-1739C>A		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000434794.1	TSL:2	c.206-266817C>A		intron	N/A	ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41737 AN: 151934 Hom.: 6204 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.0491

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.274 AC: 41738 AN: 152054 Hom.: 6203 Cov.: 32 AF XY: 0.270 AC XY: 20095 AN XY: 74320

African (AFR) AF: 0.205 AC: 8519 AN: 41494

American (AMR) AF: 0.232 AC: 3545 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1371 AN: 3470

East Asian (EAS) AF: 0.0490 AC: 253 AN: 5162

South Asian (SAS) AF: 0.225 AC: 1082 AN: 4814

European-Finnish (FIN) AF: 0.296 AC: 3127 AN: 10560

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22743 AN: 67966

Other (OTH) AF: 0.299 AC: 631 AN: 2108

Alfa AF: 0.313 Hom.: 29420

Bravo AF: 0.266

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.62
DANN	Benign	0.61
PhyloP100		-0.60
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: rs9287315; hg19: chr2-142006662;