chr2-140239515-C-G

Variant names:

• chr2-140239515-C-G
• rs1238324748
• NM_018557.3:c.13342G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018557.3(LRP1B):​c.13342G>C​(p.Val4448Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRP1B NM_018557.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.08
• Publications: 0 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]

ENSG00000300471 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.13342G>C	p.Val4448Leu	missense	Exon 88 of 91	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.13342G>C	p.Val4448Leu	missense	Exon 88 of 91	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000437977.5	TSL:5	c.2035G>C	p.Val679Leu	missense	Exon 15 of 17	ENSP00000415052.1	H0Y7T7
	LRP1B	ENST00000442974.1	TSL:5	c.649G>C	p.Val217Leu	missense	Exon 6 of 7	ENSP00000393859.1	H7C0A8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.094	T
Eigen	Benign	0.093
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.19
Sift	Benign	0.043	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.39	B
Vest4		0.89
MutPred		0.41		Loss of sheet (P = 0.0011)
MVP		0.12
MPC		0.22
ClinPred		0.66	D
GERP RS		5.5
Varity_R		0.20
gMVP		0.63
Mutation Taster		=81/19	polymorphism

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: rs1238324748; hg19: chr2-140997084;