rs765318312

Variant names:

• chr4-185374340-C-A
• rs765318312
• NM_001377440.1:c.452G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-185374340-C-A
• chr4-185374340-C-G
• chr4-185374340-C-T

Variant summary

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

The NM_001377440.1(LRP2BP):​c.452G>T​(p.Arg151Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,094 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: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: LRP2BP NM_001377440.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

Genes affected

LRP2BP (HGNC:25434): (LRP2 binding protein) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRP2BP-AS1 (HGNC:):

SNX25 (HGNC:21883): (sorting nexin 25) Predicted to enable type I transforming growth factor beta receptor binding activity. Involved in negative regulation of pathway-restricted SMAD protein phosphorylation; negative regulation of transforming growth factor beta receptor signaling pathway; and receptor catabolic process. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

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=0.086076915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP2BP	NM_001377440.1	c.452G>T	p.Arg151Leu	missense_variant	Exon 5 of 9	ENST00000505916.6	NP_001364369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP2BP	ENST00000505916.6	c.452G>T	p.Arg151Leu	missense_variant	Exon 5 of 9	2	NM_001377440.1	ENSP00000426203.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74284

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.;T;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.89	.;D;D;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.086	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;M;.
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.060
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.11	T;T;T;.
Polyphen		0.030	B;B;B;.
Vest4		0.42
MutPred		0.59		Loss of MoRF binding (P = 0.0152);.;Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);
MVP		0.33
MPC		0.37
ClinPred		0.52	D
GERP RS		1.9
Varity_R		0.11
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765318312; hg19: chr4-186295494;