chr2-140700401-C-G

Variant names:

• chr2-140700401-C-G
• rs193921022
• NM_018557.3:c.6648G>C

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.6648G>C​(p.Glu2216Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 0.121
• 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]

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=0.1733852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.6648G>C	p.Glu2216Asp	missense_variant	Exon 41 of 91	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.6258G>C	p.Glu2086Asp	missense_variant	Exon 41 of 91		XP_016859830.1
LRP1B	XM_047444771.1	c.6759G>C	p.Glu2253Asp	missense_variant	Exon 41 of 77		XP_047300727.1
LRP1B	XM_017004342.1	c.1500G>C	p.Glu500Asp	missense_variant	Exon 12 of 62		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.6648G>C	p.Glu2216Asp	missense_variant	Exon 41 of 91	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.0054	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.12
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.083	B
Vest4		0.43
MutPred		0.20		Loss of loop (P = 0.1242);
MVP		0.52
MPC		0.25
ClinPred		0.78	D
GERP RS		1.5
Varity_R		0.22
gMVP		0.53
Mutation Taster		=70/30	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: rs193921022; hg19: chr2-141457970;