Variant 6-149853053-C-T 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_032832.6(LRP11):c.721G>A(p.Val241Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,612,558 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

LRP11
NM_032832.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.399

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:

(HGNC:):

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=0.024314284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRP11	NM_032832.6 linkuse as main transcript	c.721G>A	p.Val241Ile	missense_variant	2/7	ENST00000239367.7	NP_116221.3
RAET1E-LRP11	NR_182438.1 linkuse as main transcript	n.2621G>A		non_coding_transcript_exon_variant	10/15
LOC124901427	XR_007059808.1 linkuse as main transcript	n.221C>T		non_coding_transcript_exon_variant	2/2
LRP11	NM_001410946.1 linkuse as main transcript	c.721G>A	p.Val241Ile	missense_variant	2/4		NP_001397875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP11	ENST00000239367.7 linkuse as main transcript	c.721G>A	p.Val241Ile	missense_variant	2/7	1	NM_032832.6	ENSP00000239367	P1	Q86VZ4-1
	ENST00000472053.2 linkuse as main transcript	n.173C>T		non_coding_transcript_exon_variant	2/2	3
LRP11	ENST00000367368.3 linkuse as main transcript	c.721G>A	p.Val241Ile	missense_variant	2/4	2		ENSP00000356338

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000156

AC:

AN:

249818

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135100

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.0000584

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.000165

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000240

AC:

350

AN:

1460342

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

726514

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000286

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000112

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000620

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000179

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

Feb 05, 2024

The c.721G>A (p.V241I) alteration is located in exon 2 (coding exon 2) of the LRP11 gene. This alteration results from a G to A substitution at nucleotide position 721, causing the valine (V) at amino acid position 241 to be replaced by an isoleucine (I). 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

0.059

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.1

DANN

Benign

0.93

DEOGEN2

Benign

0.0079

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.055

Sift

Benign

0.21

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.012

B;B

Vest4

0.10

MVP

0.10

MPC

0.23

ClinPred

0.024

GERP RS

-5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.090

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