Variant 4-185372920-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001377440.1(LRP2BP):c.739G>A(p.Gly247Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

LRP2BP
NM_001377440.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP2BP	NM_001377440.1 linkuse as main transcript	c.739G>A	p.Gly247Arg	missense_variant	7/9	ENST00000505916.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP2BP	ENST00000505916.6 linkuse as main transcript	c.739G>A	p.Gly247Arg	missense_variant	7/9	2	NM_001377440.1	P1	Q9P2M1-1
LRP2BP	ENST00000328559.11 linkuse as main transcript	c.739G>A	p.Gly247Arg	missense_variant	6/8	1		P1	Q9P2M1-1
LRP2BP	ENST00000510776.5 linkuse as main transcript	c.661G>A	p.Gly221Arg	missense_variant	5/7	1
LRP2BP-AS1	ENST00000514884.1 linkuse as main transcript	n.242+1855C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

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:

0.000621

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000187

AC:

AN:

251370

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000118

AC:

173

AN:

1461354

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000112

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

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 13, 2021

The c.739G>A (p.G247R) alteration is located in exon 6 (coding exon 6) of the LRP2BP gene. This alteration results from a G to A substitution at nucleotide position 739, causing the glycine (G) at amino acid position 247 to be replaced by an arginine (R). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

T;.;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.1

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.15

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.86

MutPred

0.53

Gain of MoRF binding (P = 0.0296);.;Gain of MoRF binding (P = 0.0296);

MVP

0.76

MPC

0.84

ClinPred

0.39

GERP RS

6.1

Varity_R

0.53

gMVP

0.86

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

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