rs372647222

Variant names:

• chr2-140274505-G-A
• rs372647222
• NM_018557.3:c.13061C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-140274505-G-A
• chr2-140274505-G-C
• chr2-140274505-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018557.3(LRP1B):​c.13061C>T​(p.Pro4354Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4354R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRP1B NM_018557.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.42
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19222692).

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.13061C>T	p.Pro4354Leu	missense	Exon 85 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.13061C>T	p.Pro4354Leu	missense	Exon 85 of 91	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000437977.5	TSL:5	c.1754C>T	p.Pro585Leu	missense	Exon 12 of 17	ENSP00000415052.1	H0Y7T7
	LRP1B	ENST00000442974.1	TSL:5	c.254C>T	p.Pro85Leu	missense	Exon 2 of 7	ENSP00000393859.1	H7C0A8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.4
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.25
Sift	Benign	0.43	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.48		Loss of disorder (P = 0.01)
MVP		0.25
MPC		0.19
ClinPred		0.59	D
GERP RS		1.5
Varity_R		0.059
gMVP		0.26
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: rs372647222; hg19: chr2-141032074;