2-140775217-G-A

Variant names:

• chr2-140775217-G-A
• rs9287300
• NM_018557.3:c.5500+881C>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.5500+881C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,614 control chromosomes in the GnomAD database, including 8,713 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 0.34 (8713 hom., cov: 29)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.637
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 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.5500+881C>T		intron	N/A	NP_061027.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.5500+881C>T		intron	N/A	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51236 AN: 151496 Hom.: 8693 Cov.: 29

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.338 AC: 51305 AN: 151614 Hom.: 8713 Cov.: 29 AF XY: 0.341 AC XY: 25218 AN XY: 74048

African (AFR) AF: 0.367 AC: 15152 AN: 41292

American (AMR) AF: 0.342 AC: 5210 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2066 AN: 5122

South Asian (SAS) AF: 0.336 AC: 1609 AN: 4792

European-Finnish (FIN) AF: 0.368 AC: 3874 AN: 10514

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21561 AN: 67898

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.324 Hom.: 25785

Bravo AF: 0.339

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.40
PhyloP100		0.64
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: rs9287300; hg19: chr2-141532786;