2-140238174-C-G

Variant names:

• chr2-140238174-C-G
• NM_018557.3:c.13538G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018557.3(LRP1B):​c.13538G>C​(p.Gly4513Ala) 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. 13/21 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. G4513V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRP1B NM_018557.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21207172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.13538G>C	p.Gly4513Ala	missense_variant	Exon 89 of 91	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.13148G>C	p.Gly4383Ala	missense_variant	Exon 89 of 91		XP_016859830.1
LRP1B	XM_017004342.1	c.8390G>C	p.Gly2797Ala	missense_variant	Exon 60 of 62		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.13538G>C	p.Gly4513Ala	missense_variant	Exon 89 of 91	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000437977.5	c.2231G>C	p.Gly744Ala	missense_variant	Exon 16 of 17	5		ENSP00000415052.1
LRP1B	ENST00000442974.1	c.*8G>C		downstream_gene_variant		5		ENSP00000393859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.092
Sift	Benign	0.089	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.012	B
Vest4		0.30
MutPred		0.52		Loss of loop (P = 0.0374);
MVP		0.26
MPC		0.20
ClinPred		0.48	T
GERP RS		4.8
Varity_R		0.063
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr2-140995743;