NM_018557.3:c.13538G>A

Variant names:

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

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>A​(p.Gly4513Asp) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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=0.11830139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.13538G>A	p.Gly4513Asp	missense_variant	Exon 89 of 91	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.13148G>A	p.Gly4383Asp	missense_variant	Exon 89 of 91		XP_016859830.1
LRP1B	XM_017004342.1	c.8390G>A	p.Gly2797Asp	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>A	p.Gly4513Asp	missense_variant	Exon 89 of 91	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000437977.5	c.2231G>A	p.Gly744Asp	missense_variant	Exon 16 of 17	5		ENSP00000415052.1
LRP1B	ENST00000442974.1	c.*8G>A		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	0.063
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.25
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.41	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.54		Loss of sheet (P = 0.1158);
MVP		0.23
MPC		0.25
ClinPred		0.34	T
GERP RS		4.8
Varity_R		0.065
gMVP		0.40

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;