rs777607055

Variant names:

• chr2-140239445-C-G
• NM_018557.3:c.13412G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-140239445-C-G
• chr2-140239445-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018557.3(LRP1B):​c.13412G>C​(p.Arg4471Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,432,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRP1B NM_018557.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.278828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.13412G>C	p.Arg4471Thr	missense_variant	Exon 88 of 91	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.13022G>C	p.Arg4341Thr	missense_variant	Exon 88 of 91		XP_016859830.1
LRP1B	XM_017004342.1	c.8264G>C	p.Arg2755Thr	missense_variant	Exon 59 of 62		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.13412G>C	p.Arg4471Thr	missense_variant	Exon 88 of 91	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000437977.5	c.2105G>C	p.Arg702Thr	missense_variant	Exon 15 of 17	5		ENSP00000415052.1
LRP1B	ENST00000442974.1	c.719G>C	p.Arg240Thr	missense_variant	Exon 6 of 7	5		ENSP00000393859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1432424 Hom.: 0 Cov.: 28 AF XY: 0.00000140 AC XY: 1 AN XY: 713192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.090
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.010	B
Vest4		0.43
MutPred		0.39		Gain of phosphorylation at R4471 (P = 0.0357);
MVP		0.13
MPC		0.38
ClinPred		0.94	D
GERP RS		4.5
Varity_R		0.26
gMVP		0.55

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: chr2-140997014;