6-149863612-C-G

Position:

chr6-149863612-C-G

Variant summary

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

The NM_032832.6(LRP11):c.409G>C(p.Glu137Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000432 in 1,458,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

LRP11
NM_032832.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

LRP11 (HGNC:16936): (LDL receptor related protein 11) Enables phosphoprotein binding activity. Predicted to act upstream of or within several processes, including response to cold; response to immobilization stress; and response to water deprivation. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRP11 links:

RAET1E-AS1 (HGNC:48994): (RAET1E antisense RNA 1)

RAET1E-AS1 links:

RAET1E-LRP11 (HGNC:):

RAET1E-LRP11 links:

Genome browser will be placed here

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=0.09650308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRP11	NM_032832.6 linkuse as main transcript	c.409G>C	p.Glu137Gln	missense_variant	1/7	ENST00000239367.7	NP_116221.3
RAET1E-AS1	NR_045126.1 linkuse as main transcript	n.115C>G		non_coding_transcript_exon_variant	1/2
RAET1E-LRP11	NR_182438.1 linkuse as main transcript	n.2513+1273G>C		intron_variant, non_coding_transcript_variant
LRP11	NM_001410946.1 linkuse as main transcript	c.409G>C	p.Glu137Gln	missense_variant	1/4		NP_001397875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP11	ENST00000239367.7 linkuse as main transcript	c.409G>C	p.Glu137Gln	missense_variant	1/7	1	NM_032832.6	ENSP00000239367	P1	Q86VZ4-1
RAET1E-AS1	ENST00000606915.1 linkuse as main transcript	n.119C>G		non_coding_transcript_exon_variant	1/2	1
LRP11	ENST00000367368.3 linkuse as main transcript	c.409G>C	p.Glu137Gln	missense_variant	1/4	2		ENSP00000356338

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00182

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000859

AC:

AN:

69818

Hom.:

AF XY:

0.0000993

AC XY:

AN XY:

40286

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000892

Gnomad NFE exome

AF:

0.0000394

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1307134

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

644236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000809

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000890

Gnomad4 NFE exome

AF:

0.00000957

Gnomad4 OTH exome

AF:

0.0000371

GnomAD4 genome

AF:

0.000132

AC:

AN:

151782

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00182

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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

Jan 23, 2024

The c.409G>C (p.E137Q) alteration is located in exon 1 (coding exon 1) of the LRP11 gene. This alteration results from a G to C substitution at nucleotide position 409, causing the glutamic acid (E) at amino acid position 137 to be replaced by a glutamine (Q). 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

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0044

T;T

Eigen

Benign

-0.087

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.097

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.82

D;D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.086

Sift

Benign

0.23

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.83

P;P

Vest4

0.095

MutPred

0.51

Gain of MoRF binding (P = 0.0436);Gain of MoRF binding (P = 0.0436);

MVP

0.54

MPC

2.8

ClinPred

0.12

GERP RS

3.8

Varity_R

0.19

gMVP

0.52

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