chr2-140233241-C-G

Variant names:

• chr2-140233241-C-G
• NM_018557.3:c.13745G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018557.3(LRP1B):​c.13745G>C​(p.Arg4582Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRP1B NM_018557.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.13745G>C	p.Arg4582Thr	missense_variant	Exon 91 of 91	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.13355G>C	p.Arg4452Thr	missense_variant	Exon 91 of 91		XP_016859830.1
LRP1B	XM_017004342.1	c.8597G>C	p.Arg2866Thr	missense_variant	Exon 62 of 62		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.13745G>C	p.Arg4582Thr	missense_variant	Exon 91 of 91	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000437977.5	c.2339G>C	p.Arg780Thr	missense_variant	Exon 17 of 17	5		ENSP00000415052.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.21
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.33		Gain of phosphorylation at R4582 (P = 0.0443);
MVP		0.16
MPC		0.38
ClinPred		0.69	D
GERP RS		5.7
Varity_R		0.32
gMVP		0.62

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-140990810;