chr3-46539186-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024512.5(LRRC2):​c.349T>A​(p.Leu117Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,613,770 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 4 hom. )

Consequence

LRRC2
NM_024512.5 missense

Scores

1
4
13

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.138
Variant links:
Genes affected
LRRC2 (HGNC:14676): (leucine rich repeat containing 2) This gene encodes a member of the leucine-rich repeat-containing family of proteins, which function in diverse biological pathways. This family member may possibly be a nuclear protein. Similarity to the RAS suppressor protein, as well as expression down-regulation observed in tumor cells, suggests that it may function as a tumor suppressor. The gene is located in the chromosome 3 common eliminated region 1 (C3CER1), a 1.4 Mb region that is commonly deleted in diverse tumors. A related pseudogene has been identified on chromosome 2. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.007152617).
BP6
Variant 3-46539186-A-T is Benign according to our data. Variant chr3-46539186-A-T is described in ClinVar as [Benign]. Clinvar id is 712053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRC2NM_024512.5 linkuse as main transcriptc.349T>A p.Leu117Met missense_variant 4/9 ENST00000395905.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC2ENST00000395905.8 linkuse as main transcriptc.349T>A p.Leu117Met missense_variant 4/91 NM_024512.5 P1
LRRC2ENST00000296144.3 linkuse as main transcriptc.349T>A p.Leu117Met missense_variant 4/91 P1
LRRC2ENST00000682605.1 linkuse as main transcriptc.349T>A p.Leu117Met missense_variant 4/9 P1

Frequencies

GnomAD3 genomes
AF:
0.00375
AC:
571
AN:
152200
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0128
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.000984
AC:
247
AN:
250996
Hom.:
3
AF XY:
0.000715
AC XY:
97
AN XY:
135678
show subpopulations
Gnomad AFR exome
AF:
0.0128
Gnomad AMR exome
AF:
0.000728
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000458
AC:
669
AN:
1461452
Hom.:
4
Cov.:
31
AF XY:
0.000426
AC XY:
310
AN XY:
727026
show subpopulations
Gnomad4 AFR exome
AF:
0.0138
Gnomad4 AMR exome
AF:
0.000784
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000107
Gnomad4 OTH exome
AF:
0.000712
GnomAD4 genome
AF:
0.00375
AC:
571
AN:
152318
Hom.:
4
Cov.:
32
AF XY:
0.00371
AC XY:
276
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0127
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.000215
Hom.:
0
Bravo
AF:
0.00428
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0116
AC:
51
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00121
AC:
147
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 10, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0031
T;T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.74
.;T
MetaRNN
Benign
0.0072
T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.9
M;M
MutationTaster
Benign
0.87
N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.014
D;D
Polyphen
1.0
D;D
Vest4
0.72
MVP
0.25
MPC
0.90
ClinPred
0.077
T
GERP RS
-3.4
Varity_R
0.47
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs34850909; hg19: chr3-46580676; API