Variant chr4-185370805-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001377440.1(LRP2BP):c.813C>G(p.Asp271Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LRP2BP
NM_001377440.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.346

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:55998): (LRP2BP antisense RNA 1)

LRP2BP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066319704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP2BP	NM_001377440.1 linkuse as main transcript	c.813C>G	p.Asp271Glu	missense_variant	8/9	ENST00000505916.6	NP_001364369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP2BP	ENST00000505916.6 linkuse as main transcript	c.813C>G	p.Asp271Glu	missense_variant	8/9	2	NM_001377440.1	ENSP00000426203	P1	Q9P2M1-1
LRP2BP	ENST00000328559.11 linkuse as main transcript	c.813C>G	p.Asp271Glu	missense_variant	7/8	1		ENSP00000332681	P1	Q9P2M1-1
LRP2BP	ENST00000510776.5 linkuse as main transcript	c.735C>G	p.Asp245Glu	missense_variant	6/7	1		ENSP00000424610
LRP2BP-AS1	ENST00000514884.1 linkuse as main transcript	n.81G>C		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727222

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:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.813C>G (p.D271E) alteration is located in exon 7 (coding exon 7) of the LRP2BP gene. This alteration results from a C to G substitution at nucleotide position 813, causing the aspartic acid (D) at amino acid position 271 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.3

DANN

Benign

0.61

DEOGEN2

Benign

0.055

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.57

.;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.12

N;.;N

MutationTaster

Benign

0.57

D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.028

Sift

Benign

0.45

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0050

B;B;B

Vest4

0.14

MutPred

0.34

Gain of glycosylation at Y272 (P = 0.0288);.;Gain of glycosylation at Y272 (P = 0.0288);

MVP

0.23

MPC

0.19

ClinPred

0.082

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.024

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over