dbSNP rs375845046: LRP2BP:p.Gly293Arg (chr4-185370741-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001377440.1(LRP2BP):c.877G>C(p.Gly293Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. G293S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LRP2BP
NM_001377440.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.601

Variant links:

Genes affected

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

LRP2BP links:

LRP2BP-AS1 (HGNC:):

LRP2BP-AS1 links:

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]

SNX25 links:

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ACMG classification

Classification made for transcript

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=0.07860333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP2BP	NM_001377440.1 link	c.877G>C	p.Gly293Arg	missense_variant	Exon 8 of 9	ENST00000505916.6	NP_001364369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRP2BP	ENST00000505916.6 link	c.877G>C	p.Gly293Arg	missense_variant	Exon 8 of 9	2	NM_001377440.1	ENSP00000426203.1	Q9P2M1-1
LRP2BP	ENST00000328559.11 link	c.877G>C	p.Gly293Arg	missense_variant	Exon 7 of 8	1		ENSP00000332681.7	Q9P2M1-1
LRP2BP	ENST00000510776.5 link	c.799G>C	p.Gly267Arg	missense_variant	Exon 6 of 7	1		ENSP00000424610.1	G5E9Z9
LRP2BP-AS1	ENST00000514884.1 link	n.17C>G		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.1

DANN

Benign

0.73

DEOGEN2

Benign

0.053

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.25

.;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

1.0

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.45

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.15

MutPred

0.55

Gain of catalytic residue at G293 (P = 0.1258);.;Gain of catalytic residue at G293 (P = 0.1258);

MVP

0.23

MPC

0.24

ClinPred

0.33

GERP RS

1.8

Varity_R

0.043

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over