chr2-140959494-G-C

Variant names:

• chr2-140959494-G-C
• rs16845023
• NM_018557.3:c.2888-7554C>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.2888-7554C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,190 control chromosomes in the GnomAD database, including 7,163 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 0.30 (7163 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 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.2888-7554C>G		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.2888-7554C>G		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000434794.1	TSL:2	c.323-7554C>G		intron	N/A	ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45713 AN: 151074 Hom.: 7163 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.302 AC: 45735 AN: 151190 Hom.: 7163 Cov.: 31 AF XY: 0.298 AC XY: 21987 AN XY: 73868

African (AFR) AF: 0.310 AC: 12798 AN: 41324

American (AMR) AF: 0.287 AC: 4355 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1352 AN: 3458

East Asian (EAS) AF: 0.462 AC: 2386 AN: 5162

South Asian (SAS) AF: 0.396 AC: 1905 AN: 4810

European-Finnish (FIN) AF: 0.188 AC: 1971 AN: 10512

Middle Eastern (MID) AF: 0.373 AC: 106 AN: 284

European-Non Finnish (NFE) AF: 0.295 AC: 19879 AN: 67472

Other (OTH) AF: 0.342 AC: 715 AN: 2092

Alfa AF: 0.137 Hom.: 200

Bravo AF: 0.313

Asia WGS AF: 0.360 AC: 1241 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.012
DANN	Benign	0.63
PhyloP100		-3.0
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: rs16845023; hg19: chr2-141717063;